Cytokine Profile Research Articles

Cytokine profiles associated with disease severity and prognosis of autoimmune pulmonary alveolar proteinosis

BackgroundPulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of surfactants in the alveoli. Most cases are classified as autoimmune PAP (APAP) because they are associated with autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). However, GM-CSF autoantibody levels are unlikely to correlate with the disease severity or prognosis of APAP. MethodsWe collected clinical records and measured 38 serum cytokine concentrations for consecutive patients with APAP. After exclusion of 21 cytokines because of undetectable levels, 17 cytokine levels were compared between low and high disease severity scores (DSSs). We also compared whole lung lavage (WLL)-free survival with cut-off values defined by receiver operating characteristic (ROC) curves of cytokine levels and WLL administration at 11 months. ResultsNineteen patients with APAP were enrolled in the study. Five were classified as DSS 1 or 2, while the others were classified as DSS 4 or 5. Comparison between DSS 1−2 and 4−5 revealed that the concentrations of IP-10 and GRO increased in the latter groups (p < 0.05). Fifteen patients underwent WLL. Comparison between those who underwent WLL within 11 months and the others showed that IP-10 and TNF-α were tended to be elevated in the former group (p = 0.082 and 0.057, respectively). The cut-off values of IP-10, 308.8 pg/mL and TNF-α, 19.1 pg/mL, defined by the ROC curves, significantly separated WLL-free survivals with log-rank analyses (p = 0.005). ConclusionsThe concentrations of IP-10 and GRO may reflect the DSSs of APAP. A combination of IP-10 and TNF-α levels could be a biomarker to predict WLL-free survival.

Cytokine profiling in 128 patients with transient abnormal myelopoiesis: a report from the JPLSG TAM-10 trial

AbstractTransient abnormal myelopoiesis (TAM) occurs in 10% of neonates with Down syndrome (DS). Although most patients show spontaneous resolution of TAM, early death occurs in ∼20% of cases. Therefore, new biomarkers are needed to predict early death and determine therapeutic interventions. This study aimed to determine the association between clinical characteristics and cytokine levels in patients with TAM. A total of 128 patients with DS with TAM enrolled in the TAM-10 study conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group were included in this study. Five cytokine levels (interleukin-1b [IL-1b], IL-1 receptor agonist, IL-6, IL-8, and IL-13) were significantly higher in patients with early death than in those with nonearly death. Cumulative incidence rates (CIRs) of early death were significantly associated with high levels of the 5 cytokines. Based on unsupervised consensus clustering, patients were classified into 3 cytokine groups: hot-1 (n = 37), hot-2 (n = 42), and cold (n = 49). The CIR of early death was significantly different between the cytokine groups (hot-1/2, n = 79; cold, n = 49; hot-1/2 CIR, 16.5% [95% confidence interval (CI), 7.9-24.2]; cold CIR, 2.0% [95% CI, 0.0-5.9]; P = .013). Furthermore, cytokine groups (hot-1/2 vs cold) were independent poor prognostic factors in the multivariable analysis for early death (hazard ratio, 15.53; 95% CI, 1.434-168.3; P = .024). These results provide valuable information that cytokine level measurement was useful in predicting early death in patients with TAM and might help to determine the need for therapeutic interventions. This trial was registered at UMIN Clinical Trials Registry as #UMIN000005418.

Bioinformatics analysis of hypoxia associated genes and inflammatory cytokine profiling in COPD-PH

Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is associated with worse clinical outcomes and decreased survival rates. In absence of disease specific diagnostic/therapeutic targets and unclear pathophysiology, there is an urgent need for the identification of potential genetic/molecular markers and disease associated pathways. The present study aims to use a bioinformatics approach to identify and validate hypoxia-associated gene signatures in COPD-PH patients. Additionally, hypoxia-related inflammatory profile is also explored in these patients.Microarray dataset obtained from the Gene Expression Omnibus repository was used to identify differentially expressed genes (DEGs) in a hypoxic PH mice model. The top three hub genes identified were further validated in COPD-PH patients, with chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL12 showing significant changes in comparison to healthy controls. Furthermore, multiplexed analysis of 10 inflammatory cytokines, tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), interleukin 1-beta (IL-1β), IL-4, IL-5, IL-6, IL-13, IL-17, IL-18 and IL-21 was also performed. These markers showed significant changes in COPD-PH patients as compared to controls. They also exhibited the ability to differentially diagnose COPD-PH patients in comparison to COPD. Additionally, IL-6 and IL-17 showed significant positive correlation with systolic pulmonary artery pressure (sPAP).This study is the first report to assess the levels of CXCL9 and CXCL12 in COPD-PH patients and also explores their link with the inflammatory profile of these patients. Our findings could be extended to better understand the underlying disease mechanism and possibly used for tailoring therapies exclusive for the disease.

Gut Microbiome and Cytokine Profiles in Post-COVID Syndrome.

Recent studies highlight the crucial role of the gut microbiome in post-infectious complications, especially in patients recovering from severe COVID-19. Our research aimed to explore the connection between gut microbiome changes and the cytokine profile of patients with post-COVID syndrome. Using 16S rRNA amplicon sequencing, we analyzed the composition of the gut microbiome in 60 COVID-19 patients over the course of one year. We also measured the levels of serum cytokines and chemokines using the Milliplex system. Our results showed that severe SARS-CoV-2 infection cases, especially those complicated by pneumonia, induce a pro-inflammatory microbial milieu with heightened presence of Bacteroides, Faecalibacterium, and Prevotella_9. Furthermore, we found that post-COVID syndrome is characterized by a cross-correlation of various cytokines and chemokines MDC, IL-1b, Fractalkine, TNFa, FGF-2, EGF, IL-1RA, IFN-a2, IL-10, sCD40L, IL-8, Eotaxin, IL-12p40, and MIP-1b as well as a shift in the gut microbiome towards a pro-inflammatory profile. At the functional level, our analysis revealed associations with post-COVID-19 in homolactic fermentation, pentose phosphate, NAD salvage, and flavin biosynthesis. These findings highlight the intricate interplay between the gut microbiota, their metabolites, and systemic cytokines in shaping post-COVID symptoms. Unraveling the gut microbiome's role in post-infectious complications opens avenues for new treatments for those patients with prolonged symptoms.

Abstract PO1-13-04: Distinct immune signatures discriminate between patients defined as exceptional survivors of metastatic breast cancer compared to those with rapidly progressing treatment resistant breast cancers

Abstract Background: "Atypical responders" can encompass three sub- categories of patients: "exceptional responders" (those with an unusually favourable treatment response), "rapid progressors" (unusually poor or no response), and "exceptional/long-term survivors" (outlived initial prognosis). Here, we aim to investigate the drivers of immune surveillance mechanisms (local, lymphoid and peripheral) and the nature of immunological tumour recognition in exceptional survivors of stage 4 metastatic disease following standard-of-care chemo- and targeted therapies. Methods: We conducted a complementary multi-platform immune profiling study to define differences in the phenotypic immune landscape including mass-spectrometry-based proteomics on peripheral blood mononuclear cells (PBMCs), multiplex cytokine profiling of patient serum, and high-dimensional flow cytometry on whole blood samples. By staining 500μl of whole blood using 2 panels, 353 immune-cell-related parameters were obtained for comparisons among the following groups: "exceptional survivors," "exceptional responders," "rapid progressors," "non-exceptional metastatic patients," "early breast cancer patients," and "healthy volunteers". Patients were matched for age, breast cancer receptor status, and sites of metastases where possible. Results: Preliminary analysis of serum biomarkers and proteome of the PBMCs of the exceptional survivors showed elevated levels of NK-cell-related proteins such as KCTD10 and RBBP7. Flow cytometry analysis revealed the presence of increased activated CD56dim NK cells, CD56bright NK cells, and central memory (CM) (CD45RA-CD27+) CD8 T cells in both the exceptional survivors and the rapid progressors. However, expression of CD25 appears to be the main mode of activation in rapid progressors compared with increased NKG2D expression in exceptional survivors. Additionally, activation of the unconventional gd T cells was evident in both groups with terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) Vd1 cell predominating in the exceptional survivors. In the rapid progressors, the increased CD25+ TEMRA Vd2 cells coupled with elevated serum IL-17A and IL-1b suggest their ability to generate IL-17. Th2 cytokines, IL-5 and IL-13 were also enriched in rapid progressors and concomitant increase in CD25+ Th2 cells reveals a strong Th2-driven immune signature in these patients. Finally increased CD86+ atypical double negative (DN) B cells, mostly comprised of the DN2 subset were also significantly enriched in the rapid progressors compared to the exceptional survivors where DN1 B cells were prevalent. Conclusion: The multi-platform approach to investigating immune responses present in atypical responders has identified several distinct immunophenotypes in which the extreme outliers differ in their potential immune surveillance mechanisms. Functional validation of these findings through activation and cytotoxicity assays is currently underway and future work aims to understand the spatial biology of these circulating immune cells within the context of their primary tumours, metastases, and lymph nodes. Citation Format: Helen Kakkassery, Thanussuyah Alaguthurai, Zuza Kozik, Paul Buckley, Ruifang Lu, Esme Carpenter, Rosalind Graham, Gheed Alhity, Farhana Hossain, Sadiyah Mukhtar, Syed Haider, Jyoti Choudhary, Sheeba Irshad. Distinct immune signatures discriminate between patients defined as exceptional survivors of metastatic breast cancer compared to those with rapidly progressing treatment resistant breast cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-04.

Cytokine and immunoglobulin profiles of Arbor Acres broiler chickens at different stages of physiological development.

Modern scientific research focuses on a detailed study of the immune system, the mechanisms of immunosuppression, and the search for an effective means to restore disturbed immune homeostasis in farm animals. The present study examined the cytokine and immunoglobulin (Ig) profiles of healthy broiler chickens during physiological development. Arbor Acres broilers (n = 28) were used in the study to achieve this objective. The immune status of broiler chickens was assessed on 7, 14, 28, and 42 days of age, including serum levels of cytokines, Igs, and lysozyme by enzyme immunoassay. We observed a decrease in the efficiency of immune system functioning of birds with increasing age. The most pronounced immunological deficiency in the body of broiler chickens is noted at the age of 7-14 days, which is associated with immaturity of the immune system and is characterized by the fact that non-specific humoral and specific cellular defense factors are at a rather low level. The levels of lysozyme, interleukin (IL)-2, IL-10, and IgA in blood serum at this age were minimal; starting from 28 days of age, there is a specific humoral immune deficiency, which is compensated by strengthening of cellular defense factors. The serum level of IgY intensively decreases against the background of an increase of lysozyme, IL-2, IL-4, and IL-10. During postnatal ontogenesis, the immune system of broiler chickens undergoes dynamic changes that have an age direction and phase character. Changes in the immune system may affect immunocompetence, disease susceptibility, and, consequently, productivity.

Cytokine profiling in pan-cancer analysis: Guiding clinical prognosis and immunotherapeutic efficacy

Cytokine profiling in pan-cancer analysis: Guiding clinical prognosis and immunotherapeutic efficacy

ANGPTL3 accelerates atherosclerotic progression via direct regulation of M1 macrophage activation in plaque

IntroductionThe N-terminal domain of angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity. Its C-terminal fibrinogen-like (FBN) domain is a ligand of macrophage integrin αvβ3. ObjectivesANGPTL3 might home to plaque where it directly regulates macrophage function via integrin αvβ3 for atherosclerosis progression. MethodsLdlr-/- mice on a high-fat diet and ApoE-/- mice on a chow diet were received adeno-associated virus (AAV)-mediated Angptl3 gene transfer and followed up for 12 weeks. ApoE-/- mice were injected AAV containing FLAG-tagged Angptl3 cDNA for tracing. Atherosclerotic features were compared between Angptl3-/-ApoE-/- mice and ApoE-/- littermates. THP-1 cells were exposed to 0 or 50 μg/ml ANGPTL3 FBN domain for 24 h to evaluate Toll-like receptor (TLR)4 expression using western blot analysis and circulating cytokine and chemokine profiles by the MILLIPLEX MAP assay. Phospho-proteomic profile was established in ANGPTL3-treated macrophages. Integrin β3 deficient THP-1 cells were obtained by sgRNAs targeting RGD sequence using Lentivirus-Cas9 system. ResultsAngptl3 overexpression increased atherosclerotic progression and CD68+ macrophages in plaque (p < 0.05 for all). By immunostaining, FLAG+ cells were identified in plaque of gene transferred ApoE-/- mice. Fluorescent immunostaining detected co-localisation of Angptl3 and CD68 in plaque macrophages. Phospho-proteomic analysis revealed that Angptl3 induced phosphorylation of proteins that were involved in the IL-17 signalling pathway in THP-1 cells. In vitro, ANGPTL3 treatment increased the production of interleukin (IL)-1β and tumour necrosis factor-α in THP-1 cells (p < 0.05 for both). Exposure of ANGPTL3 to THP-1 cells induced Akt phosphorylation which was weakened in integrin β3 deficient ones. ANGPTL3 elevated TLR4 expression via Akt phosphorylation. In response to lipopolysaccharide, nuclear factor-κB activity was 2.2-fold higher in THP-1 cells pre-treated with ANGPTL3 than in untreated cells (p < 0.05). ConclusionsTargeting ANGPTL3 could yield a dual benefit of lowering lipid levels in the blood and suppressing macrophage activation in plaque.

Immune response to inactivated bacterial vector carrying the recombinant K39 antigen of Leishmania infantum in mice

Objective: To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum, and a purified antigen. Methods: Mice were subjected to the following treatments: (1) Purified recombinant K39 (rK39) protein at a 20 μg dose with complete Freund’s adjuvant; (2) Inactivated Escherichia coli (BL21 DE3) carrying the K39 protein at an equivalent total protein content of 200 μg; (3) Inactivated bacteria lacking the K39 protein; (4) Non-immunized control animals. Serological monitoring was performed. All groups were challenged by intraperitoneal injection of 107 Leishmania infantum promastigotes. After euthanasia, the liver and spleen were collected to analyze the levels of TNF, IFN-γ, IL-12, IL-4, and IL-10. Results: Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins. The IgG1 subclass was the predominant immunoglobulin; however, the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response. Conclusions: The inactivated bacterial vector carrying the K39 antigen, as well as the purified antigen can induce a long-lasting immune response in immunized mice, predominantly favouring a Th2 profile response.

Th1/Th2 cytokines in early peripheral blood of patients with multiple injuries and its predictive value for SIRS: A bioinformatic analysis

This study aims to evaluate the changes in helper T lymphocyte (Th)1/Th2 factor levels in peripheral blood of patients with severe multiple injuries and their prognostic value for nosocomial infection using bioinformatic analysis. The experimental group consisted of 180 patients with numerous injuries admitted to our hospital between January 2021 and June 2023, with 80 healthy volunteers serving as controls. Th1 cytokines (interleukin-2 and interferon-γ) and Th2 cytokines (IL-4 and IL-10) were evaluated 48 hours after admission using enzyme-linked immunosorbent assays. The experimental group was separated into two groups: those with systemic inflammatory response syndrome (SIRS) and those without SIRS, for cytokine analysis and SIRS incidence. Furthermore, the study examined Th1 and Th2 cytokine levels in trauma patients in various body locations within the experimental group. A receiver operating characteristic (ROC) curve analysis was performed to determine the predictive value of Th1/Th2 cytokines for SIRS incidence. The experimental group had lower IL-2 and IFN-γ levels compared to the control group, but greater levels of IL-4 and IL-10. There were no significant variations in Th1 and Th2 cytokine levels across the experimental groups. Patients with SIRS had lower levels of IL-2 and IFN-γ but greater levels of IL-4 and IL-10 compared to those without SIRS. Combined cytokine levels have a better predictive value for SIRS than individual cytokines alone. In conclusion, individuals with severe multiple injuries had a change from Th1 to Th2 cytokine profiles, which was most evident in those with SIRS. The combined cytokine levels had a substantial predictive value for SIRS incidence in this patient cohort.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1β, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.

Kinetics of IFNγ-Induced Cytokines and Development of Immune-Related Adverse Events in Patients Receiving PD-(L)1 Inhibitors.

Immune checkpoint inhibitors (ICI) have the potential to trigger unpredictable immune-related adverse events (irAEs), which can be severe. The underlying mechanisms of these events are not fully understood. As PD-L1 is upregulated by IFN, the heightened immune activation resulting from PD-1/PD-L1 inhibition may enhance the IFN response, triggering the expression of IFN-inducible genes and contributing to irAE development and its severity. In this study, we investigated the interplay between irAEs and the expression of IFN-inducible chemokines and cytokines in 134 consecutive patients with solid tumours treated with PD-(L)1 inhibitors as monotherapy or in combination with chemotherapy or other immunotherapy agents. We compared the plasma levels of IFN-associated cytokines (CXCL9/10/11, IL-18, IL-10, IL-6 and TGFβ) at various time points (at baseline, at the onset of irAE and previous to irAE onset) in three patient groups categorized by irAE development and severity: patients with serious irAEs, mild irAEs and without irAEs after PD-(L)1 inhibitors. No differences were observed between groups at baseline. However, patients with serious irAEs exhibited significant increases in CXCL9/10/11, IL-18 and IL-10 levels at the onset of the irAE compared to baseline. A network analysis and correlation patterns highlighted a robust relationship among these chemokines and cytokines at serious-irAE onset. Combining all of the analysed proteins in a cluster analysis, we identified a subgroup of patients with a higher incidence of serious irAEs affecting different organs or systems. Finally, an ROC analysis and a decision tree model proposed IL-18 levels ≥ 807 pg/mL and TGFβ levels ≤ 114 pg/mL as predictors for serious irAEs in 90% of cases. In conclusion, our study elucidates the dynamic changes in cytokine profiles associated with serious irAE development during treatment with PD-(L)1 inhibitors. The study's findings offer valuable insights into the intricate IFN-induced immune responses associated with irAEs and propose potential predictive markers for their severity.

Analysis of the Protective Effects of Rosa roxburghii-Fermented Juice on Lipopolysaccharide-Induced Acute Lung Injury in Mice through Network Pharmacology and Metabolomics.

Acute lung injury, a fatal condition characterized by a high mortality rate, necessitates urgent exploration of treatment modalities. Utilizing UHPLS-Q-Exactive Orbitrap/MS, our study scrutinized the active constituents present in Rosa roxburghii-fermented juice (RRFJ) while also assessing its protective efficacy against LPS-induced ALI in mice through lung histopathological analysis, cytokine profiling, and oxidative stress assessment. The protective mechanism of RRFJ against ALI in mice was elucidated utilizing metabolomics, network pharmacology, and molecular docking methodologies. Our experimental findings demonstrate that RRFJ markedly ameliorates pathological injuries in ALI-afflicted mice, mitigates systemic inflammation and oxidative stress, enhances energy metabolism, and restores dysregulated amino acid and arachidonic acid metabolic pathways. This study indicates that RRFJ can serve as a functional food for adjuvant treatment of ALI.

Short-Term Panax Ginseng Extract Supplementation Reduces Fasting Blood Triacylglycerides and Oxygen Consumption during Sub-Maximal Aerobic Exercise in Male Recreational Athletes.

Ginseng, a popular herbal supplement among athletes, is believed to enhance exercise capacity and performance. This study investigated the short-term effects of Panax ginseng extract (PG) on aerobic capacity, lipid profile, and cytokines. In a 14-day randomized, double-blind trial, male participants took 500 mg of PG daily. Two experiments were conducted: one in 10 km races (n = 31) and another in a laboratory-controlled aerobic capacity test (n = 20). Blood lipid and cytokine profile, ventilation, oxygen consumption, hemodynamic and fatigue parameters, and race time were evaluated. PG supplementation led to reduced total blood lipid levels, particularly in triacylglycerides (10 km races -7.5 mg/dL (95% CI -42 to 28); sub-maximal aerobic test -14.2 mg/dL (95% CI -52 to 23)), while post-exercise blood IL-10 levels were increased (10 km 34.0 pg/mL (95% CI -2.1 to 70.1); sub-maximal aerobic test 4.1 pg/mL (95% CI -2.8 to 11.0)), and oxygen consumption decreased during the sub-maximal aerobic test (VO2: -1.4 mL/min/kg (95% CI -5.8 to -0.6)). No significant differences were noted in race time, hemodynamic, or fatigue parameters. Overall, PG supplementation for 2 weeks showed benefits in blood lipid profile and energy consumption during exercise among recreational athletes. This suggests a potential role for PG in enhancing exercise performance and metabolic health in this population.

Mechanism of isoflurane‑mediated breast cancer growth in vivo.

Use of volatile anesthetics is associated with worse outcome following tumor resection surgery compared with the use of intravenous anesthetics. However, the underlying mechanism has not been clearly delineated yet in vivo. The EO771 cell-based congenic breast cancer model was used in the present study. Isoflurane directly binds to and inhibits two adhesion molecules, leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1). Similarly, exposure to sevoflurane, another volatile anesthetic and LFA-1 inhibitor, is associated with an increase in breast cancer size compared with non-exposure. Thus, the present study first examined the role of LFA-1 and Mac-1 in the EO771 breast cancer model. Both LFA-1 deficiency and inhibition enhanced tumor growth, which was supported by cytokine and eicosanoid data profiles. By contrast, Mac-1 deficiency did not affect tumor growth. The exposure to isoflurane and sevoflurane was associated with an increase in breast cancer size compared with non-exposure. These data suggested that isoflurane enhanced tumor growth by interacting with LFA-1. Isoflurane exposure did not affect tumor growth in LFA-1-deficient mice. In summary, the present data showed that LFA-1 deficiency facilitated breast cancer growth, and isoflurane, an LFA-1 inhibitor, also increased breast cancer growth.

Mycobacterium avium paratuberculosis Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis.

Vitamin D plays a vital role in modulating both innate and adaptive immune systems. Therefore, vitamin D deficiency has been associated with higher levels of autoimmune response and increased susceptibility to infections. CYP27B1 encodes a member of the cytochrome P450 superfamily of enzymes. It is instrumental in the conversion of circulating vitamin D (calcifediol) to active vitamin D (calcitriol). This is a crucial step for macrophages to express Cathelicidin Anti-microbial Peptide (CAMP), an anti-bacterial factor released during the immune response. Our recent study indicated that a Crohn's disease (CD)-associated pathogen known as Mycobacterium avium paratuberculosis (MAP) decreases vitamin D activation in macrophages, thereby impeding cathelicidin production and MAP infection clearance. The mechanism by which MAP infection exerts these effects on the vitamin D metabolic axis remains elusive. We used two cell culture models of THP-1 macrophages and Caco-2 monolayers to establish the effects of MAP infection on the vitamin D metabolic axis. We also tested the effects of Calcifediol, Calcitriol, and SB203580 treatments on the relative expression of the vitamin D metabolic genes, oxidative stress biomarkers, and inflammatory cytokines profile. In this study, we found that MAP infection interferes with vitamin D activation inside THP-1 macrophages by reducing levels of CYP27B1 and vitamin D receptor (VDR) gene expression via interaction with the TLR2-dependent p38/MAPK pathway. MAP infection exerts its effects in a time-dependent manner, with the maximal inhibition observed at 24 h post-infection. We also demonstrated the necessity to have toll-like receptor 2 (TLR2) for MAP infection to influence CYP27B1 and CAMP expression, as TLR2 gene knockdown resulted in an average increase of 7.78 ± 0.88 and 13.90 ± 3.5 folds in their expression, respectively. MAP infection also clearly decreased the levels of p38 phosphorylation and showed dependency on the p38/MAPK pathway to influence the expression of CYP27B1, VDR, and CAMP which was evident by the average fold increase of 1.93 ± 0.28, 1.86 ± 0.27, and 6.34 ± 0.51 in their expression, respectively, following p38 antagonism. Finally, we showed that calcitriol treatment and p38/MAPK blockade reduce cellular oxidative stress and inflammatory markers in Caco-2 monolayers following macrophage-mediated MAP infection. This study characterized the primary mechanism by which MAP infection leads to diminished levels of active vitamin D and cathelicidin in CD patients, which may explain the exacerbated vitamin D deficiency state in these cases.

Manual therapy and exercise effects on inflammatory cytokines: a narrative overview.

Matching disease and treatment mechanisms is a goal of the Precision Medicine Initiative. Pro- and anti-inflammatory cytokines (e.g., Tumor Necrosis Factor-alpha, Transforming Growth Factor-beta, and Interleukin-2, 10, and 12) have gained a significant amount of interest in their potential role in persistent pain for musculoskeletal (MSK) conditions. Manual therapy (MT) and exercise are two guideline-recommended approaches for treating MSK conditions. The objective of this narrative overview was to investigate of the effects of MT and exercise on pro- and anti-inflammatory cytokines and determine the factors that lead to variability in results. Two reviewers evaluated the direction and variabilities of MT and exercise literature. A red, yellow, and green light scoring system was used to define consistencies. Consistencies in responses were seen with acute and chronic exercise and both pro- and anti-inflammatory cytokines. Chronic exercise is associated with a consistent shift towards a more anti-inflammatory cytokine profile (Transforming Growth Factor-beta, and Interleukin-2 and 13, whereas acute bouts of intense exercise can transiently increase pro-inflammatory cytokine levels. The influence of MT on cytokines was less commonly studied and yielded more variable results. Variability in findings is likely related to the subject and their baseline condition or disease, when measurement occurs, and the exercise intensity, duration, and an individual's overall health and fitness.

The Impact of Yoga on Cancer Survivorship: A Scoping Review

Background: As cancer survival rates improve, survivors face numerous physical and psychological challenges. Yoga, an ancient practice integrating physical, mental, and spiritual health, has shown potential in alleviating cancer treatment-related symptoms and enhancing overall health. Methods: This scoping review conducted a comprehensive literature search across multiple databases, focusing on randomized trials that assessed yoga’s effects on cancer survivors post-treatment. The review spanned studies published between 2018 and 2022, emphasizing physical and psychosocial benefits. Results: Eight randomized trials were identified, demonstrating yoga’s diverse benefits across physical and psychological dimensions. Significant findings include reductions in depression, improvements in shoulder mobility, pain, and anxiety, management of cancer-related fatigue, sleep quality, and modulation of inflammatory cytokine profiles, suggesting holistic benefits in managing cancer side effects. Conclusion: Yoga presents a holistic, low-risk intervention that significantly improves quality of life, manages fatigue, and supports psychological well-being in cancer survivors. Future research should investigate yoga’s therapeutic potential and develop personalized interventions for survivors’ recovery and long-term well-being.

Effect of propofol and isoflurane on NK Cells: A pilot study on perioperative breast cancer patients from Eastern India

Introduction: In onco-anesthesiology, the selection between intravenous and volatile anesthetics for maintaining NK cell response during cancer surgery has been an ambiguous area. In the absence of any such comparative Indian report, this pilot study aimed to investigate the effect of intravenous anesthetic, Propofol, and volatile anesthetic, Isoflurane on the NK cell-mediated immune-inflammatory response of perioperative breast cancer patients. Materials and Methods: Treatment naive breast cancer patients (N, 50) selected for surgery were randomly subjected to either Isoflurane (N, 25) or Propofol (N, 25) anesthetic group. The peripheral blood samples were collected 1 day before surgery (Pre), 1 h after incision (Intra) and 48 h after surgery (Post). The blood samples were subjected to immunophenotyping, activation, degranulation, and cytokine analysis. Results: The frequency of NK cell populations did not differ between the Isoflurane and Propofol groups irrespective of cancer stage II/III. NK cell degranulation marker CD107a and activation marker CD335 expression were significantly reduced in the postoperative period compared to the preoperative group in the Isoflurane group but Propofol did not inflict such alterations. Both Isoflurane/Propofol elicited similar trends in the cytokine profiles of interleukin (IL)-6, IL-15, interferon (IFN)-g and transforming growth factor (TGF)-β levels. Isoflurane significantly increased IL-8 during the intraoperative period and matrix metalloproteinase (MMP)-9 during the postoperative period whereas no such changes were observed with Propofol. Conclusion: This pilot study indicated that Propofol partially proved better over Isoflurane in maintaining the activation (CD335) and degranulation of NK cells (CD107a) and alleviating inflammation (IL-8 and MMP-9) during the perioperative period in the breast cancer patients.

Characteristics of the cytokine profile in patients with a new coronavirus infection with chronic hepatitis C

The aim was to assess individual cytokine profile parameters in patients with new coronavirus infection combined with chronic hepatitis C, depending on the severity of COVID-19 and liver fibrosis. Materials and Methods: A comparative study of laboratory and instrumental data of 147 patients with COVID-19 and CHC, comprising the first group; the second group consisted of 81 patients with COVID-19, and the third - of 94 patients with CHC. Patients in the first and second groups were divided into subgroups based on the severity of COVID-19, as well as the degree of liver fibrosis. Results: It was established that 73% of patients with a combination of COVID-19 and CHC during the peak of the new coronavirus infection had an increase in the levels of several cytokines compared to similar indicators in patients with CHC without COVID-19. In addition, the values of certain cytokines significantly differed from those of patients with COVID-19, regardless of the severity of the disease. It was also noted that in patients with a combination of COVID-19 and CHC with severe progression of the new coronavirus infection, the values of certain cytokines were higher than in patients with COVID-19 alone. Furthermore, in the group of patients with a combination of COVID-19 and CHC, an increase in the values of certain cytokines was observed as liver fibrosis progressed.