Changes In Cytokine Profile Research Articles

Intratumoral injection of schwannoma with attenuated Salmonella typhimurium induces antitumor immunity and controls tumor growth

Schwannomas are slow-growing benign neoplasms that develop throughout the body causing pain, sensory/motor dysfunction, and death. Because bacterial immunotherapy has been used in the treatment of some malignant neoplasms, we evaluated attenuated Salmonella typhimurium strains as immunotherapies for benign murine schwannomas. Several bacterial strains were tested, including VNP20009, a highly attenuated strain that was previously shown to be safe in human subjects with advanced malignant neoplasms, and a VNP20009 mutant that was altered in motility and other properties that included adherence and invasion of cultured mammalian cells. VNP20009 controlled tumor growth in two murine schwannoma models and induced changes in cytokine and immune effector cell profiles that were consistent with induction of enhanced innate and adaptive host immune responses compared with controls. Intratumoral (i.t.) injection of S. typhimurium led to tumor cell apoptosis, decreased tumor angiogenesis, and lower growth of the injected schwannoma tumors. Invasive VNP20009 was significantly more efficacious than was a noninvasive derivative in controlling the growth of injected tumors. Bacterial treatment apparently induced systemic antitumor immunity in that the growth of rechallenge schwannomas implanted following primary bacterial treatment was also reduced. Checkpoint programmed death-1 (PD-1) blockade induced by systemic administration of anti-PD-1 antibodies controlled tumor growth to the same degree as i.t. injection of S. typhimurium, and together, these two therapies had an additive effect on suppressing schwannoma growth. These experiments represent validation of a bacterial therapy for a benign neoplasm and support development of S. typhimurium VNP20009, potentially in combination with PD-1 inhibition, as a schwannoma immunotherapy.

Paroxysmal nocturnal hemoglobinuria: advances in the understanding of pathophysiology, diagnosis, and treatment

In recent years, "old" paroxysmal nocturnal hemoglobinuria (PNH) has achieved new advances in terms of the understanding of its pathophysiology, modern approach to diagnostics, optimization of therapy, and dynamic development of new therapeutic agents. This review emphasizes the greater than previously recognized importance of the reduced susceptibility of PNH stem cells to apoptosis in the selection of a defective clone. Some changes in cytokine and chemokine profiles in patients with PNH have been interpreted in the context of autoimmunity and apoptosis. The classification of PNH presentations, characteristics of the functions of selected glycosylphosphatidylinositol-anchored proteins, as well as pathologies associated with hemolysis, thrombosis, and bone marrow failure are described. The current diagnostic process for various forms of PNH is presented in detail, as well as its importance in the choice of treatment and prognosis of the disease course. Determinants of modern treatment, such as strategies (complement C5 inhibitors vs hematopoietic stem cell allotransplantation), the safety and efficacy of treatment with eculizumab or ravulizumab, policy of initiation and monitoring of treatment, the criteria for response to treatment and final outcomes of treatment are described. Among the new therapeutic agents, crovalimab and C5 inhibitors at a less advanced stage of research are discussed: tesidolumab, pozelimab, zilucoplan, nomacopan, and cemdisiran. The first approved proximal complement pathway inhibitors that primarily prevent extravascular hemolysis, pegcetacoplan, danikopan, and iptacopan, are presented and their potential benefits are highlighted.

Primary dental care treatment in primary Sjögren's syndrome: a possible role in improving salivary flow rate.

Primary Sjögren's syndrome (pSS) is an inflammatory chronic disorder that mainly affects exocrine glands. Additionally, oral infections can aggravate the glandular dysfunction. However, data on primary dental care (PDC) treatment in pSS are scarce. This study aimed to appraise the impact of PDC on the Xerostomia Inventory (XI), unstimulated/stimulated salivary flow rates and salivary cytokine profile in pSS. Fifty-two pSS patients and 52 sex- and age-matched control participants without systemic autoimmune diseases were included in a prospective study. At inclusion, all participants were assessed through a standardised protocol, measurement of salivary pro-inflammatory cytokines, and underwent PDC. Dental procedures included: oral hygiene guidance, restorative treatment of caries, surgical removal of residual roots and impacted or partially erupted teeth, cysts, supra and subgingival periodontal scaling and treatment of soft tissue disorders (removal of lesions and treatment of opportunistic infections). After 3 months, the clinical/laboratorial assessments were repeated. At inclusion, the Decayed, Missing and Filled Teeth (DMFT) index was higher in the pSS patients than in the control group (13.3±8.2 vs. 8.6±6.2, p=0.002), whereas periodontal parameters were comparable in both groups (p>0.05). After PDC, 26.9% of pSS patients showed a reduction of at least 6 points (clinical improvement) in XI, but mean XI remained unchanged (p=0.285). PDC resulted in an increase in mean unstimulated (p<0.001) and stimulated (p=0.001) salivary flow rates in pSS, with no change in salivary cytokine profile (p≥0.05). PDC promoted improvement in unstimulated and stimulated salivary flow rates in pSS. This novel finding reinforces the recommendation of this strategy for pSS patients. gov (Identifier: NCT03711214).

Serum cytokine profile of pregnant women with malaria, intestinal helminths and HIV infections in Ibadan, Nigeria.

Malaria, helminthiasis and HIV are widespread in developing countries taking a heavy toll on pregnant women. Due to similar environmental and human factors of transmission, they co-exist. The epidemiology and pathology of these diseases have been extensively studied but data on serum cytokine profile changes which is crucial in pregnancy is limited. The aim of this study was to evaluate the co-infections and their impact on peripheral blood cytokines. Blood and stool samples were collected from recruited 18-45-year-old pregnant women in different trimesters who were apparently healthy with no obvious complications in pregnancy. Pretested questionnaires were administered for personal and socio-demographic details. Malaria parasitemia in Giemsa-stained thick blood films was examined microscopically. Stool samples were screened for helminths using Kato-Katz method. Cytokine levels of TNF-α, IFN-γ, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and IL-17 in 121 serum samples were determined using ELISA. Data were analysed using descriptive statistics and Mann-Whitney U test at α0.05. Relative to the single infections, there were significant reductions in IFN-γ and IL-13 in second and third trimesters respectively in those with Plasmodium and helminth co-infection. IFN-γ and IL-17 were elevated while IL-1α and IL-12p70 were reduced in co-infection of helminths and HIV. Co-infection of Plasmodium and HIV in second and third trimesters showed significant elevations in IL-1α, IL-10 and IL-17 while TNF-α, IL-4 and IL-12p70 were significantly reduced. HIV in pregnancy and its co-infection with Plasmodium resulted in significant distortions in the cytokine profile. However, helminth and its co-infection with Plasmodium or HIV produced less changes in the cytokine profile.

Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients.

ObjectiveTo explore dynamic changes of cytokines and virological markers associated with hepatitis B surface antigen (HBsAg) loss during peginterferon alpha-2a (PEG-IFN α-2a) treatment in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients.MethodsIt was a single-center prospective cohort study. HBeAg-positive CHB patients were prospectively and consecutively enrolled. Cytokines were detected at baseline, week 12 and 24 of PEG-IFN treatment. HBsAg disappearance rate was the primary evaluation index at 48 weeks of PEG-IFN treatment.ResultsAmong 100 patients who completed the 48-week PEG-IFN α-2a treatment, 38 patients achieved serum HBeAg disappearance, 25 patients achieved HBeAg seroconversion, 9 patients achieved functional cure, 37 patients had HBsAg decline of ≥1 log IU/ml, and 8 patients produced hepatitis B surface antibody (HBsAb). Albumin (ALB), fms-like tyrosine kinase 3 ligand (FLT3-L) and interferon-alpha2 (IFN-α2) in the clinical cure group were significantly lower than those in the non-clinical-cure group at baseline. After 12 weeks of treatment, HBsAg in the clinical cure group was significantly lower than that in the non-clinical-cure group (median 1.14 vs. 3.45 log10IU/ml, Z=-4.355, P < 0.001). The decrease of HBsAg and hepatitis B virus desoxyribose nucleic acid (HBV DNA) in the clinical cure group was significantly higher than that in non-clinical-cure group (median: HBsAg 1.96 vs. 0.33 log10IU/ml, Z=-4.703, P< 0.001; HBV DNA 4.49 vs.3.13 log10IU/ml, Z=-3.053, P=0.002). The increase of IFN-α2 in the cure group was significantly higher than that in the non-clinical-cure group (497.89 vs. 344.74, Z=-2.126, P=0.034). After 24 weeks of treatment, HBsAg, HBeAg, Flt3-L, and IL-10 in the clinical cure group were significantly lower than those in the non-clinical-cure group (median: HBsAg 0.70 vs. 3.15 log10IU/ml, Z=-4.535, P< 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, P = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, P=0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, P < 0.001). HBsAg decreased significantly in the clinical cure group compared with non-clinical-cure group (median 3.27 vs. 0.45, Z=-4.463, P < 0.001).ConclusionDynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.

The Memory Benefit to Aged APP/PS1 Mice from Long-Term Intranasal Treatment of Low-Dose THC.

THC has been used as a promising treatment approach for neurological disorders, but the highly psychoactive effects have largely warned off many scientists from pursuing it further. We conducted an intranasal treatment using low-dose THC on 12-month-old APP/PS1 mice daily for 3 months to overcome any potential psychoactive response induced by the systemic delivery. Our results demonstrate that the THC nasal treatment at 0.002 and 0.02 mg/kg significantly slowed the memory decline compared to that in the vehicle-treated transgenic mouse control group. An enzyme-linked immunosorbent assay showed that the Aβ1–40 and 1–42 peptides decreased in the THC-treated groups. The Western blot data indicate that long-term low-dose THC intranasal administration promoted p-tau level reduction and mitochondrial function marker redistribution. The blood biochemical parameter data demonstrate some insignificant changes in cytokine, immunoglobulin, and immune cell profiles during intranasal THC treatment. Intranasal delivery is a non-invasive and convenient method that rapidly targets therapeutics to the brain, minimizing systemic exposure to avoid unwanted adverse effects. Our study provides new insights into the role of low-dose THC intranasal treatment as a pharmacological strategy to counteract alterations in Alzheimer’s disease-related cognitive performance.

Abstract P1-04-12: Pathway analysis of immune checkpoint gene regulation as altered in Type 2 diabetes: Implications for breast cancer patients treated with checkpoint inhibitors

Abstract Background: Mediators of immune exhaustion are an active area of breast cancer research. Type II diabetes mellitus (T2D), the most common metabolic disorder, both increases breast cancer incidence and decreases survival. Despite this clear link, impacts of the T2D immune phenotype on cancer remain poorly understood. We have previously demonstrated that the chronic inflammatory state of T2D leads to immune exhaustion, but how the T2D breast microenvironment interacts with T cells is unclear. Exosomes are crucial components of intercellular communication and are associated with increased breast cancer aggressiveness. Given this function, we hypothesized that T2D adipocyte-derived exosomes drive T cell exhaustion. Here, we characterize expression patterns and regulatory networks driving T2D immune phenotypes. Methods: Exosomes were first isolated from culture media of mature human primary breast adipocytes from, either insulin-sensitive (IS), or rendered insulin-resistant (IR) by ex vivo TNFα-treatment. Human primary peripheral blood mononuclear cells (PBMCs) from nondiabetic (ND) and T2D donors were stimulated ex vivo with plate bound anti-CD3 (5 ug/ml) and soluble CD28 (2 ug/ml) for 48 hours and treated with exosomes. Different small molecule inhibitors of the bromo and extraterminal (BET) protein family, including the pan-BET inhibitor JQ1 and the BRD4-selective PROTAC degrader MZ-1, were used to identify BET protein-regulated targets. We also used the AMP-activating protein kinase (AMPK) inhibitor Compound-C to identify the role of this pathway in activating this major epigenetic player. Multicolor flow cytometry was subsequently performed with an LSRII cytometer to assess expression of inhibitory receptors PD-1, CTLA-4, TIM-3 and TIGIT on immune subsets. Events for live cells were analyzed in FlowJo. Cytokines were collected from conditioned media and analyzed via Th17 cytokine staining panel. Results: We observed that exosomes derived from IR breast adipocytes increase expression of immune exhaustion markers in CD4+ and CD8+ T cells, compared to IS or ND matched controls. Additionally, we define signal transduction among BET proteins, AMPK signaling, and immune checkpoint expression. Lastly, we identify changes in cytokine profile between IS and IR treated groups. Taken together, our findings suggest a network of immune regulation imparted by exosomes. Impacts: Metabolic health does not inform the current standard of care in breast medical oncology, which contributes to a large, underserved population in which treatment plans are not well established or optimized for their comorbidities. Our findings offer a deeper understanding of immune checkpoint regulation in T2D and suggest new insights into treatment of diabetic breast cancer patients. Citation Format: Christina S. Ennis, Pablo LLevenes, Manohar Kolla, Naser Jafari, Anna C Belkina, Gerald V. Denis. Pathway analysis of immune checkpoint gene regulation as altered in Type 2 diabetes: Implications for breast cancer patients treated with checkpoint inhibitors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-04-12.

Cytokine profile and oxidative stress parameters in women with initial manifestations of pelvic venous insufficiency

&lt;abstract&gt; &lt;p&gt;Pelvic venous insufficiency (PVI) in women is widespread and is closely associated with the risk of reproductive disorders (in 15–25% of patients) and a high rate of the disease recurrence after treatment. The factors involved in venous wall damage include atherogenic stimuli and chronic endotoxin aggression due to inflammatory processes. The changes in the initial stages of the disease are usually minor and selective. There is currently an urgent need to identify initial markers of these changes to develop preventive measures for their correction. Therefore, the aim of this study was to determine the cytokine profile parameters' levels, as well as the activity of lipid peroxidation (LPO) and antioxidant defense (AOD) reactions in women with initial manifestations of PVI. Thirty-nine female patients with PVI (mean age 37.4 ± 9.1 years old) were the subjects of the study. The diagnosis was verified by clinical and instrumental examination including ultrasound angioscanning of the pelvic veins and therapeutic and diagnostic laparoscopy, and it was finally confirmed histologically. The control group included 30 nearly healthy women (mean age 33.5 ± 6.3 years old) who underwent surgical sterilization by laparoscopic access. Spectrophotometric, fluorometric and immunoassay methods were used in the study. The cytokine profile in female patients with PVI, as compared to the control group, was characterized by an increased concentration of proinflammatory (interleukin (IL) (IL-6) and IL-8) and anti-inflammatory cytokines (IL-4 and IL-10) and higher ratio values (IL-6/IL-10). The level of primary LPO products, conjugated dienes, was significantly increased and level of final products TBARs values was decreased in comparison to the control. The AOD system main enzyme activity, superoxide dismutase (SOD), was decreased, while the catalase activity increased. In patients with PVI, the glutathione reduced form concentration was lower than in the control group. The results of the study in women with PVI suggest negative changes in the cytokine profile and multidirectional changes in the indicators of the LPO system state in the initial stages of the disease. The control of these changes in patients with PVI should probably be an important component of preventive measures in the initial stages of the disease.&lt;/p&gt; &lt;/abstract&gt;

Skin Substitute Preparation Method Induces Immunomodulatory Changes in Co-Incubated Cells through Collagen Modification.

Chronic ulcerative and hard-healing wounds are a growing global concern. Skin substitutes, including acellular dermal matrices (ADMs), have shown beneficial effects in healing processes. Presently, the vast majority of currently available ADMs are processed from xenobiotic or cadaveric skin. Here we propose a novel strategy for ADM preparation from human abdominoplasty-derived skin. Skin was processed using three different methods of decellularization involving the use of ionic detergent (sodium dodecyl sulfate; SDS, in hADM 1), non-ionic detergent (Triton X-100 in hADM 2), and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We next evaluated the immunogenicity and immunomodulatory properties of this novel hADM by using an in vitro model of peripheral blood mononuclear cell culture, flow cytometry, and cytokine assays. We found that similarly sourced but differentially processed hADMs possess distinct immunogenicity. hADM 1 showed no immunogenic effects as evidenced by low T cell proliferation and no significant change in cytokine profile. In contrast, hADMs 2 and 3 showed relatively higher immunogenicity. Moreover, our novel hADMs exerted no effect on T cell composition after three-day of coincubation. However, we observed significant changes in the composition of monocytes, indicating their maturation toward a phenotype possessing anti-inflammatory and pro-angiogenic properties. Taken together, we showed here that abdominoplasty skin is suitable for hADM manufacturing. More importantly, the use of SDS-based protocols for the purposes of dermal matrix decellularization allows for the preparation of non-immunogenic scaffolds with high therapeutic potential. Despite these encouraging results, further studies are needed to evaluate the beneficial effects of our hADM 1 on deep and hard-healing wounds.

Subgingival Microbiota and Cytokines Profile Changes in Patients with Periodontitis: A Pilot Study Comparing Healthy and Diseased Sites in the Same Oral Cavities.

Periodontitis is a common condition characterized by an exacerbated pro-inflammatory response, which leads to tissue destruction and, ultimately, alveolar bone loss. In this pilot study, we assess the microbiota composition and cytokine profile changes in patients with stage III/IV, grade B/C periodontitis, specifically by comparing healthy and diseased sites in the same oral cavity. Overall, we found that microbiota architecture was significantly disrupted between diseased and healthy sites, and that the clustering was driven, in part, by the increased relative abundances of Synergistetes in diseased sites, as well as the increased abundances of Firmicutes in healthy sites. We also observed that diseased sites were enriched in Synergistetes, TM7, SR1, Spirochaetes, Bacteroidetes and Fusobacteria, and depleted in Firmicutes, Proteobacteria, Tenericutes and Actinobacteria compared to healthy sites. We found that Interleukin-1b, Interleukin-4, Interleukin-10, and Interleukin-17A were significantly overexpressed in diseased sites, whereas Interleukin-6 and TNF-alpha do not differ significantly between healthy and diseased sites. Here, we observed concomitant changes in the subgingival plaque microbiota and cytokines profile, suggesting that this combined alteration could contribute to the pathobiology of periodontitis.

Early Interferon-Gamma Response in Nonhuman Primate Recipients of Solid-Organ Xenotransplantation

To understand changes in biological responses in nonhuman primate (NHP) recipients of xenotransplantation (XTP), we retrospectively investigated chronological changes in cytokine profiles of NHP recipients after solid-organ XTP. Plasma samples were collected from 7 NHP recipients of pig heart or kidney XTP with α-1,3-galactosyltransferase gene knockout (GTKO)under anti-CD154-based immune suppression at the following time points: immediately before; 2 hours, 3 days, and 7 days after XTP; and weekly thereafter until the graft failed. The plasma levels of the following cytokines were measured: interleukin (IL)-1α, IL-1β, IL-6, IL-12p70, IL-8, IL-10, IL-15, tumor necrosis factor, interferon gamma (IFN-γ), D-dimer, C3a, and histone-complexed DNA fragments. For in vitro experiments, human natural killer (NK) cells were cocultured with wild-type porcine endothelial cells (PECs), GTKO-PECs, and human umbilical vein endothelial cells, with or without anti-CD154 antibody. IFN-γ levels in the culture supernatants were compared. IFN-γ levels peaked on day 7 or 10 of XTP and then decreased to basal levels, whereas proinflammatory cytokine levels increased along with the elevation of histone-complexed DNA fragments and were sustained until xenograft failure. In vitro, human NK cells produced more IFN-γ when in contact with wild-type PECs than with human umbilical vein endothelial cells, which was not reduced by the use of GTKO-PECs or addition of anti-CD154 antibody to the mixture. In NHP recipients of XTP, the early peak of IFN-γ priming subsequent inflammatory responses may be attributed to NK cell activation in response to xenografts.

Resveratrol regulates cytokine secretion by cardiac microvascular endothelium under hypoxia/reoxygenation condition

Abstract Background Microvascular endothelial injury is recently considered playing an initial role in myocardial ischemia/reperfusion injury (MIRI). Cardiac microvascular endothelial cells (CMECs) regulate cardiomyocytes and haematocytes via secreting cytokine. MIRI jeopardize not only the barrier function but also the paracrine function of microvasculature. Resveratrol, a natural polyphenolic compound, was demonstrated to protect myocardium against MIRI and to preserve the function of endothelium. However, how the paracrine function of CMECs is regulated by MIRI and resveratrol remains to be elucidated. Purpose The study was to illuminate the alteration of cytokine profiles secreted by CMECs under hypoxia/reoxygenation (H/R) condition and its modulation by resveratrol. Methods CMECs were exposed to different concentrations of resveratrol for 30 minutes and then were subjected to H/R for 12 h/2 h. Apoptotic rates were measured to determine the optimal concentration. Protein antibody arrays were performed to find the alteration of cytokine secreted into conditioned medium by CMECs. A Gene Ontology (GO) analysis was applied to interpret the functional implication of changes in cytokine profiles. Results Resveratrol inhibited apoptosis of CMECs in a dose-dependent manner after H/R and reached its peak effect at the concentration of 100μM, which reduced apoptosis from 27.27±2.95% to 15.01±1.36% (Figure 1A and B). The results of a cluster analysis and all significantly altered factors are shown in figure 1C (fold-change &amp;gt;1.5; p&amp;lt;0.05). Twenty-nine types of cytokine were significantly changed by H/R (15 factors decreased and 14 increased, Figure 2A), and resveratrol at 100μM changed 98 types of cytokine compared with the H/R group (93 factors decreased and 5 increased, Figure 2B). Among these cytokine, eight factors were increased by H/R and they were decreased by resveratrol. Eleven were attenuated by H/R and further decreased by resveratrol. Insulin-like growth factor binding protein-1 was up-regulated by H/R and it was further increased by resveratrol (Figure 2C). The factors with significant alteration were involved in cellular growth, proliferation and differentiation, as well as chemotaxis and transport. Conclusions Resveratrol inhibited the apoptosis of CMECs and modulated the paracrine function of cardiac microvascular endothelium under ischemia/reperfusion condition. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation Figure 1Figure 2

The Influence of Sanatorium-Resort Rehabilitation on the Cytokine Profile and Quality of Life Parameters in Juvenile Rheumatoid Arthritis

Aim. To study was to assess the dynamics of cytokine profile indicators and quality of life in patients with juvenile rheumatoid arthritis under the influence of the standard sanatorium-resort rehabilitation complex. Material and methods. At the stage of sanatorium rehabilitation, 112 patients aged from 8 to 17 years (mean age 13.2±3.7) with juvenile rheumatoid arthritis were examined. The dynamics of the main quality of life indicators were assessed using the CHAQ questionnaire (pediatric version). Changes in proinflammatory (TNF-α, IL-1, IL-6) and anti-inflammatory cytokines (IL-4, IL-10) were evaluated in correlation with quality of life indices. The control group consisted of 25 healthy equals in age. Results. In juvenile rheumatoid arthritis, the cytokine profile changes, expressed in significantly higher indices of both pro- and antiinflammatory cytokines associated with functional disorders and, as a consequence, lower quality of life indicators as compared with healthy equals in age. Under the influence of sanatorium-resort treatment, functional disorders decreased, quality of life increased, levels of TNF-α, IL-1 as well as anti-inflammatory cytokine IL-4 significantly (p&lt;0,05) decreased. As for other both pro- and antiinflammatory cytokines, only non-significant tendency to decrease was registered. Conclusion. It has been established that before the beginning of sanatorium-resort treatment, the quality of life parameters were lower in patients with juvenile rheumatoid arthritis (JRA), while the values of both proinflammatory (TNF-α, IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines were significantly (p&lt;0,01) higher than in the control group. At the same time, changes in the studied parameters correlated with the activity of the inflammatory process and the severity of the functional insufficiency of the joints. There were noted the positive influence of the standard complex of sanatorium-resort treatment on the examined quality of life parameters and the tendency to normalization of cytokine profile indexes in patients with JRA.

P–417 A comparison of baseline and sequential changes of extended cytokine profile during implantation window between women who did and did not conceive after embryo transfer

Abstract Study question To compare the changing peripheral levels of inflammation-related cytokine profile during a 9-day period after blastocyst transfer between women who did and did not conceive. Summary answer:Successful implantation is associated with transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy.What is known already: Immunomodulation is thought to be important for the prevention of rejection of the implanting semi-allograft embryo and successful establishment of pregnancy. A successful pregnancy is characterized by a dominance of anti-inflammatory cytokine profile in the peripheral blood in the first and second trimesters of pregnancy. It is achieved by a complex interplay between various immune cells and cytokines at the fetal-maternal interface, among which the key-players are interleukine–10 (IL–10) and transforming growth factor-β1 (TGF-β1). The circulating inflammatory response in the first few days after embryo transfer to the pathophysiology of implantation failure remains unclear. Study design, size, duration: This prospective observational and longitudinal study on 47 women with infertility was performed in an in vitro fertilization unit from December 2018 to August 2019. The amounts of a range of cytokines was measured on serial blood samples obtained during a 9-day period after blastocyst transfer. Participants/materials, setting, methods Serial blood samples were obtained on the day of embryo transfer, and 3, 6, and 9 days afterward for measurement of serum interferon gamma (IFN-γ), tumor necrosis factor alpha, interleukin (IL)–2, IL–4, IL–10, IL–12, IL–13, IL–17, IL–18, and IL–22 using cytometric bead arrays; transforming growth factor beta 1 (TGF-β1) was measured using commercial enzyme-linked immunosorbent assay kits. Main results and the role of chance The cytokine profile was similar between the women who conceived and those who did not on the day of blastocyst transfer. In women who conceived, IFN-γ and IL–17 (pro-inflammatory cytokines) exhibited a transient and significant increase on day 3 after blastocyst transfer, which decreased to the baseline levels by day 6. Meanwhile, IL–10 (anti-inflammatory cytokine) was increased significantly on days 6 and 9, and TGF-β1 (anti-inflammatory cytokine) was increased significantly on day 9 after blastocyst transfer. In women who did not conceive, there was a more pronounced increase in IFN-γ and IL–17 (pro-inflammatory cytokines) on day 3, which was sustained on days 6 and 9 without a switch to an anti-inflammatory cytokine profile. Among women who conceived after blastocyst embryo transfer, there was a transient and modest increase in serum pro-inflammatory cytokine profile (IFN-γ and IL–17) 3 days after blastocyst transfer, which was followed by a switch to anti-inflammatory cytokine profile (increase IL–10 and TGF-β1) by 6 days after blastocyst transfer and the latter increase was sustained 9 days after blastocyst transfer, when pregnancy was confirmed. Limitations, reasons for caution This is an observational study on peripheral blood cytokine levels, so it is not possible to draw conclusions if the implantation failure is due primarily to failure of the embryo to elicit a trigger for the switch or failure of maternal response to a normal trigger released by the embryo. Wider implications of the findings: The characteristic change in peripheral cytokine profile during successful implantation, well before confirmation of pregnancy, may provide an opportunity to develop serum biomarkers to monitor implantation and to understand the mechanism of its failure, especially in women who experience recurrent implantation failure after IVF. Trial registration number Not applicable

English

Bovine respiratory diseases are widespread and too costly disease impacting contributes to economically essential diseases like mastitis and pneumonia worldwide. The present study aimed to explore the influence of M. bovis field strain 07801 on the status of PBMCs in the challenged cattle group and the immunized one. For this aim, the PBMCs proliferation, apoptosis, and cytokine profile changes were determined. In this study, M. bovis strain Mb 07801 and reference strain PG45 were used; ten calves (2-3 months old) were arranged into two groups (5 calve each): 1) PBS-challenged group (with M. bovis 07801 at about 1010 CFU/ml), and 2) immunized group (by Inactivated M. bovis 07801); both groups were treated nasally and intra-tracheal. Blood samples were obtained from both groups and examined for PBMCs proliferation and apoptosis, as well as serum cytokine profile, before infection and at day zero and days 7, 14, 21, and 36 post bacterial treatment. The results revealed that M. bovis strain (07801and PG45) antigen increased the proliferative response of the stimulated PBMC compared with the unstimulated cells and ConA-alone stimulated. The PBMC apoptosis showed a non-significant increase in both challenged and immunized groups compared to the negative and positive control (treated with apoptosis inducer) groups. Besides, the levels of cytokines profile showed a significant up-regulation in IFN-γ, IL-4, IL-2, IL-18, TNF-α, IFN-α, IL-6, IL-10 IL-1β, and IL-13, in both groups, except IL-4 and IL-18 those recorded a down-regulation in the immunized group at days 7,14, 21, and 36 post-M. bovis infection. In conclusion, immunization markedly ameliorated the immune deterioration induced by M. bovis strain 07801.

COVID-19, T Cells, Cytokines and Immunotherapy: Review

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus (COVID-19), materialized in the city of Wuhan and quickly spread to form a global pandemic. An essential role in the immune system is undertaken by lymphocytes, which defend against bacteria, viruses, fungi, and parasites. Previous study found that very severe COVID-19 patients had suppression of the immune response enabling the virus to spread and cause more damage. This was evident by the changes in their white blood cell and lymphocyte count. Early clinical findings suggest that those suffering from severe COVID-19 have reduced numbers of lymphocytes, monocytes, and other granulocytes. One of the most efficient responses for a variety of viral infections is cellular immune response activation, especially via T cells. Viruses can be eliminated by T cytotoxic (CD8+) (Tc) in the host body, these secrete a variety of molecules, including interferons (IFNs), granzyme, and perforin. T helper (CD4+) (Th) cells help by assisting cytotoxic T cells and B cells to eliminate viral infection. CD8+ and CD4+ work together in a coordinated immune response with other constituents to primarily resolve acute viral infections, and after to produce protection against any reinfection.&#x0D; Also, COVID-19 causes dramatic changes in cytokine profiles and serological markers. Therefore, the subsets of immune cells and the level of the pro-inflammatory cytokines are crucial evidence to determine the severity of COVID-19. The disease severity has already been proved to be associated with the disruption in the proinflammatory chemokine response, this eventually leads to a cytokine storm and progression of cytokines release syndrome (CRS). This review aimed to demonstrate a full understanding of the alterations to the immune response by determining the T-cell expression and cytokine levels against the pathological processes of COVID-19, which can be a significant step in early treatment and diagnosis of this disease, in reduction of COVID-19 mortality cases, and to emphasize the most recent and current studies to try to identify new immuno-therapeutics for COVID-19.

Оценка эффективности метода микроинъекционной аутотрансплантации тканей на основе иммунологических показателей

Relevance of the topic. Chronic radiation damage to the rectum occurs in 5-10% of patients. The development and application of a method for treating patients with post-radiation rectal injuries using autologous regenerative cells of adipose tissue in a clinic will make it possible to achieve high results in treatment. Purpose – to conduct a comparative analysis of the effectiveness of the method of microinjection autotransplantation of tissues based on immunological parameters. Patients and methods. The study involved 66 patients – women aged 28 to 83 years inclusive with complications of radiation therapy (rectovaginal fistulas, radiation proctitis, radiation ulcers). We carried out a comparative analysis of the condition of patients with post-radiation injuries before and after treatment, and also evaluated the role of microinjection autotransplantation of tissues in the treatment of post-radiation injuries of the rectum. The results and effectiveness of treatment were judged by changes in the main immunological parameters. Results. Our results indicate the high efficiency of the method of microinjection autotransplantation of adipose tissue in the treatment of post-radiation damage to the rectum. Impaired repair of damaged tissue in patients with post-radiation damage to the rectum is accompanied by changes in the T-cell level of immunity and an imbalance of pro- and anti-inflammatory cytokines, which leads to a decrease in reparation capabilities, prolonged non-healing of the defect, and progression of the disease. The revealed changes in cellular immunity and cytokine profile are mutually aggravating. At the same time, the use of SVF makes it possible to normalize these indicators, and, accordingly, allows achieving sustainable results in treatment, reducing the risk of complications, and preventing the likelihood of relapses. All this will allow in a short time to objectively assess the somatic status of the patient, the degree of operational risk, choose the most adequate treatment tactics, predict the outcome of treatment in each specific case, and will also give high clinical results (elimination of inflammation, epithelialization of the defect), and will improve the quality of life of patients. Conclusion. The use of SVF will not only eliminate the pathology, but also prevent further relapses by stimulating the regenerative capabilities of the affected tissues, as well as by achieving an immunostimulating, anti-inflammatory effect.

Predicting the development of complications in patients with rhinosinusitis by cytokine profile indicators

Aim. To develop a method for predicting the development of complications in rhinosinusitis patients based on the cytokine profile study.&#x0D; Methods. We examined 110 patients with rhinosinusitis and 30 healthy donors (control group). The patients were divided into the group without a complicated course of rhinosinusitis (first group, n=65) and the group with a complicated course of rhinosinusitis (second group, n=45). The blood serum levels of interleukin (IL)-1, IL-4, IL-8, IL-10, IL-17, IL-18, interferon (IFN)- were determined by enzyme immunoassay. Statistical analysis of the results was performed by using Microsoft Excel 2013 and Statistica 12.0 software. Statistically significant differences between the compared groups were determined by using the MannWhitney U-test, and p 0.05 was considered significant. Multivariate analysis included correlation analysis and stepwise regression analysis. The mathematical model consistency was determined by using Fisher's F-test, and p 0.05 was considered significant.&#x0D; Results. Changes in cytokine profile manifested by a decrease in the level of interleukin-1 (p=0.00001), interleukin-4 (p=0.045) and an increase in the level of interleukin-18 (p=0.00001) were revealed in patients with uncomplicated course of rhinosinusitis. The complicated course of rhinosinusitis was characterized by a decrease in the level of interleukin-1 (p=0.00002), interleukin-4 (p=0.049) and an increase in the level of interleukin-8 (p=0.023), interleukin-17 (p=0.00015) and interleukin-18 (p=0.0002). Comparative analysis of the first and the second groups of patients showed an increased level of interleukin-8 (p=0.00001), interleukin-17 (p=0.0001) and reduced levels of interleukin-18 (p=0.00045) in the group of patients with complicated course of rhinosinusitis. Based on interleukin-17, interleukin-8 and interleukin-18 levels, the mathematical model for predicting the development of complications in patients with rhinosinusitis was developed.&#x0D; Conclusion. The complicated course of rhinosinusitis was characterized by decreased levels of interleukin-1, interleukin-4 and increased levels of interleukin-17, interleukin-8 and interleukin-18, indicating a more pronounced inflammatory process; for personalized therapy, an approach based on interleukin-17, interleukin-8 and interleukin-18 levels was developed on which the development of a complicated course in patients with rhinosinusitis can be predicted.

Effect of a Moderate Weight Loss on Serum Fetuin-A and Markers of Inflammation in Individuals With Obesity

ObjectivesElevated fetuin-A (Fet-A) has been shown to be a risk factor for several metabolic diseases and understanding the effects of moderate weight loss on changes in Fet-A and other inflammatory markers could allow for lifestyle intervention strategies. The association of inflammatory markers and Fet-A with incremental body weight loss is unknown. The objective of the study was to evaluate the association of inflammatory markers, including TNF-alpha (TNF-α), adiponectin, and C-reactive protein (CRP), Fet-A, and it’s phosphorylated form, pFet-A, with incremental body weight loss. MethodsSixteen men achieved a targeted weight loss of 8% to 10% of initial body weight. In this study, we analyzed changes in serum TNF-α, adiponectin, and CRP inflammatory cytokines to changes in serum serum-Fet-A and pFet-A. We also examined the relationship of changes in cytokine profile to alterations in anthropometrics and other metabolic indices. All statistical analyses were performed using GraphPad Prism version 8.0. ResultsA moderate body weight loss of 8% to 10%, significantly decreased serum CRP, but did not affect TNF-α or adiponectin concentrations in individuals with obesity. Serum CRP started to decrease with 4% to 6% body weight loss, demonstrating a mean change in serum CRP concentrations of – 0.15 mg/L and – 0.10 mg/L, for 4%-6% and 8%-10% body weight loss, respectively, for each 1 kg of body weight loss. Weight-loss induced change in serum CRP concentrations were not significantly associated with a decrease in serum Fet-A or pFet-A, although a trend was observed for change in serum pFet-A (r = 0.44, P = 0.09). ConclusionsA moderate weight loss improved serum inflammatory marker C-reactive protein but did not affect TNF-α or adiponectin concentrations in individuals with obesity. These changes were not significantly associated with a decrease in serum pFet-A although a trend was observed. Funding SourcesThis work was supported by the American Diabetes Association (ADA 7–04-JF-36); the Alabama Agricultural Experiment Station (ALA080–052).

Cytokine and Chemokine Profile Changes in Patients with Neovascular Age-Related Macular Degeneration After Intravitreal Ranibizumab Injection for Choroidal Neovascularization.

ObjectiveTo investigate the concentrations of cytokine and chemokines profiling in aqueous humor for choroidal neovascularization (CNV) due to neovascular age-related macular degeneration (nAMD) before and during Intravitreal injection of ranibizumab (IVR) and its relation with the disease’s active state.MethodsThe cytokine levels in aqueous humour were detected by the Bio-Plex® 200 System and the Bio-Plex™ Human Cytokine Standard 27-Plex, Group I. Aqueous humour samples of experimental group were collected from 19 patients diagnosed nAMD at baseline and at 1 month after IVR. Aqueous humour samples of control group were collected from 20 patients undergoing cataract surgery.ResultsAqueous humor levels of basic fibroblast growth factor (basic FGF) and RANTES were significantly lower in nAMD patients than in the control group (P=0.044 and P<0.001, respectively). Vascular endothelial growth factor-A (VEGF-A) was significantly higher in nAMD patients than in the control group (P < 0.001). The average Eotaxin levels were significantly higher in nAMD patients after IVR than before (P=0.03). Contrarily, the average VEGF-A levels were significantly lower in AMD patients after IVR than before (P < 0.001).ConclusionAngiogenic, growth factors and inflammatory are involved in the formation of neovascularization of AMD patients. IVR did not cause significant differences in any growth factors or inflammatory cytokines in nAMD patients with the exception of VEGF.