Interleukin Profile Research Articles

Potential of Pre-Operative Serum Interleukin-6 as a Biomarker for Colorectal Cancers

The diagnosis of colorectal cancers (CRC) at its early stage is challenging due to lack of early markers. Current diagnostic tests are either invasive or show low sensitivity. Interleukins are known to elevate and play important roles in the development and progression of the CRC. The studies on interleukin profiles of CRC patients are mainly confined to Caucasian populations while South Asian data are sparse. Therefore, the aim of this study was to investigate the serum IL-6 and IL-10 levels in a cohort of Sri Lankan CRC patients and explore their potential to be used as markers for early diagnosis/prognosis of CRC. Blood samples from 35 CRC patients and 35 healthy volunteers were obtained after informed consent. Their clinical findings and carcinoembryonic antigen (CEA) levels were recorded. Concentrations of IL-6 and IL-10 were measured using ELISA according to manufacturer’s protocols. Mean serum [IL-6] was found to be significantly higher in CRC patients than controls (p<0.05). The mean [IL-10]showed no difference to that of controls. (p>0.05). Interestingly, the [IL-6] in CRC patients were correlated with the disease stage (Stage I-0.16pg/ml; stage II-7.01pg/ml; stage III-15.8pg/ml and stage IV-35.48pg/ml). CEA levels were not correlated with the disease stage or withIL-6 levels. This study provided preliminary evidence to use IL-6 as a potential biochemical marker for the diagnosis of CRC inaddition to CEA. Furthermore, IL-6 could be a marker for prognosis of CRC. Further studies with higher patient samples are needed to validate the results of this study.

Геронтологические особенности влияния новой коронавирусной инфекции на показатели интерлейкинового профиля, воспаления и эндогенной интоксикации у пациентов зрелого и пожилого возраста с ишемической болезнью сердца

Background: Coronary heart disease (CHD) is considered as an independent risk factor for COVID19, however, the indicators of inflammation and endogenous intoxication in patients with CHD 3-4 weeks after recovery from COVID-19 have not been the subject of scientific research. The aim of the study: Assessment of the gerontological features of the effect of the transferred new coronavirus infection on the indicators of the interleukin profile, inflammation and endogenous intoxication of mature and elderly patients with coronary heart disease in the early stages of recovery. Materials and methods: The study included 58 mature-age patients with coronary heart disease 3-4 weeks after recovery from COVID-19 of moderate severity, who made up the comparison group. The main group of patients was represented by 62 elderly people with coronary heart disease who had suffered a new coronavirus infection and were examined in the same way as the previous group, 3-4 weeks after recovery. The level of C-reactive protein and highly sensitive C-reactive protein in the blood was studied using the Nicomed-reader express analyzer, and antistreptolysin-O was studied using an immunoturbidimetric method on the Cobas 600 analyzer (Switzerland). The blood levels of bilirubin, urea, creatinine and sialic acids were studied using the ROKI biochemical analyzer. The content of systemic cytokines was determined by the Beckton Dickinson FACS Canto 2 (USA). The level of anxiety and depression was studied on the HADS scale. Results: 3-4 weeks after recovery from COVID-19, antistreptolysin-O levels ranged from 120.9 МЕ/ml to 208.1 МЕ/ml. Significant changes among the considered parameters of inflammation and endogenous intoxication in patients with coronary heart disease in old age during recovery from a new coronavirus infection were accompanied by a change in the content of highly sensitive C-reactive protein in peripheral blood. In the early stages of recovery after COVID-19, in elderly patients with coronary heart disease, the concentration of many studied cytokines in blood plasma remained elevated compared with those aged 45-59 years. The excess of reference values in both groups was found for IL-17, TNF-α and IFN-α, and among elderly patients – for IL-3, IL-4, IL-6, IL-7, IL-17. Conclusion: Antistreptolysin-O, highly sensitive C-reactive protein, C-reactive protein can be considered markers of recovery in patients with combined coronary heart disease in the early stages after a new coronavirus infection.

Clinical and immunological efficacy of complex therapy for bronchial asthma in children with the inclusion of components of far eastern brown algae

Classical basic therapy for asthma is aimed at stopping inflammation, primarily atopic, and has achieved significant positive results in the treatment of the disease, which has led to a decrease in the severity of asthma. The proportion of patients in whom asthma control is achieved does not exceed 30%; complete control is achieved in 5%, that is associated with the influence non-atopic factors on the pathogenesis of BA, leading to the search for additional methods of correction. Despite the identified biological, immunomodulatory properties of the components of brown algae, the mechanisms of their action, in asthma, are not sufficiently illuminated, which became the purpose of this study: to determine the possible immunomodulatory effect of a functional food product in children with asthma based on brown algae (Far Eastern kelp) and its use in addition to standard therapy to improve control of the course of this disease. Children with asthma (n = 56) aged from 5 to 17 years were comprehensively examined and divided into 2 groups: those who received a functional food product in addition to standard therapy (n = 20) and those who received only standard therapy (n = 36). Laboratory tests included CBC, immunogram, cytokines (IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL- 10, IL-18, TNFá), blood ICC MPM, and herpesvirus DNA. Against the background of complex treatment, changes in the interleukin profile (IL-6, IL-10, IL-18) were noted, characteristic of a decrease in the intensity of inflammatory processes, including nonspecific ones, expressed in a tendency towards a decrease in the total number of lymphocytes, an increase in the immunoregulatory index both due to an increase in the number of T helper cells and and reduction of killer T cells. This was confirmed by a decrease in monocytes and ESR. Improved energy supply of immunocompetent blood cells (granulocytes and monocytes), a decrease in the number of patients with active replication of EBV and herpes virus type 6 indicate its immunomodulatory effect. The result of these changes was the positive clinical dynamics of asthma control indicators, which allows us to recommend the inclusion of a functional food product based on Far Eastern brown algae in addition to standard therapy for children with asthma aged 5-17 years.

Distribution and risk factors of Trichomonas vaginalis infection with relevance to interleukin profile among population in Duhok city, Iraq

BackgroundVaginal trichomoniasis is a sexually transmitted disease causes adverse health outcomes, the causative agent is Tichomonas vaginalis. Infected women develop abnormal vaginal discharge with vaginitis. While, men mostly suffer from prostatitis and urethritis. ObjectivesThis study aimed to detect the rate of T.vaginalis infection in association with risk factors, measurement of blood parameters, interleukine-2 (IL-2) and interleukine-8(IL-8) levels among individuals. MethodsA total of 500 females were tested, a vaginal swab and blood were collected from the participants, and they were within the age range of 18–70 years old. High vaginal swabs were examined microscopically using wet mount preparation, the blood used for measurement of blood parameters using coulter count machine and IL-2 and IL-8 levels were evaluated using ELISA technique. ResultsOut of 500 individuals, the prevalence of T. vaginalis infection was 45(9.0 %). The maximum infection rates were reported among age group (18–28) years, rural residents, illiterates, married women (16.7 %), (15.9 %),(30.0 %),(11.7 %),respectively. Moreover, high positivity of infection revealed among low economical level 12.5 % compared to only 1.7 % in high economy group. Unemployed women, those with bad vaginal hygiene showed high incidence of infection 10.5 % and 6.3 %, respectively. It was noted a significant decrease in red blood cells and hemoglobin concentration, however, there was a significantly increased in white blood cells among infected subjects. Furthermore, the levels of both interleukin-2 and interleukin-8 were significantly higher among infected individuals compared to healthy ones. ConclusionsEffective strategies for disease awareness are needed and should include health promotion, education, and prevention.

Differences in the Interleukin Profiles in Inattentive ADHD Prepubertal Children Are Probably Related to Conduct Disorder Comorbidity.

Inflammatory cytokines are involved in attention deficit hyperactivity disorder (ADHD), a highly prevalent neurodevelopmental disorder. To quantify the baseline levels of pro- and anti-inflammatory cytokines and their changes after methylphenidate (MPH), a total of 31 prepubertal children with ADHD were recruited and subclassified into only two ADHD presentations-ADHD attention deficit (n = 13) or ADHD combined (n = 18). The children were also screened for oppositional defiant conduct disorder (ODCD) and anxiety disorder. Blood samples were drawn at 09:00 and after 4.63 ± 1.87 months of treatment. Four pro-inflammatory cytokines (interleukin-1beta (IL-1β), IL-5, IL-6, tumor necrosis factor-alpha (TNF-α)) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were measured using a Luminex® assay. For statistics, a factorial analysis was performed in Stata 15.1. Overall, there were no statistically significant differences in the interleukin (IL) values induced by treatment. When grouped by presentation, the differences were present almost exclusively in ADHD-AD, usually with a profile opposite to that observed in ADHD-C, and with interactions between comorbid factors, with IL-1β (p = 0.01) and IL-13 (p = 0.006) being the ones reaching the greatest statistical significance. These differences are probably related to the ODCD factor, and they disappear after treatment. In conclusion, the changes observed in cytokine levels in prepubertal children only in the ADHD-AD presentation are probably related to comorbidities (specifically ODCD) and are mitigated after treatment.

Starvation and Inflammation Modulate Adipose Mesenchymal Stromal Cells' Molecular Signature.

Mesenchymal stromal cells (MSCs) and their released factors (secretome) are intriguing options for regenerative medicine approaches based on the management of inflammation and tissue restoration, as in joint disorders like osteoarthritis (OA). Production strategy may modulate cells and secretome fingerprints, and for the latter, the effect of serum removal by starvation used in clinical-grade protocols has been underestimated. In this work, the effect of starvation on the molecular profile of interleukin 1 beta (IL1β)-primed adipose-derived MSCs (ASCs) was tested by assessing the expression level of 84 genes related to secreted factors and 84 genes involved in defining stemness potential. After validation at the protein level, the effect of starvation modulation in the secretomes was tested in a model of OA chondrocytes. IL1β priming in vitro led to an increase in inflammatory mediators' release and reduced anti-inflammatory potential on chondrocytes, features reversed by subsequent starvation. Therefore, when applying serum removal-based clinical-grade protocols for ASCs' secretome production, the effects of starvation must be carefully considered and investigated.

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.

Evaluation of Interleukin-1β, Interleukin-6 and Interleukin-10 Profiles in Serum and Surgically Created Wound Exudates of Alloxan-Induced Diabetic Rabbits

The knowledge of immune-modulatory actions of interleukins could be of immense value in the management of diabetic wounds. This study evaluated the interleukin profiles of diabetic wounded rabbits. Sixteen New Zealand White rabbits of mean weight 2.5 ± 0.7 kg used for this study were divided into four groups; A, B, C and D, of four rabbits each; A (non-diabetic and non-wounded) as control, B (diabetic and non-wounded, C (wounded and non-diabetic) and D (wounded and diabetic). Three (3) cm2 skin wounds were created in a standard aseptic procedure while diabetes was induced by administration of alloxan monohydrate. Serum and wound exudate were harvested on days 0, 3, 7, 14, 21 and 28 for Interleukin-1β, Interleukine-6 and Interleukine-10 assays. The increases in the serum concentration of Interleukin-1β and Interleukine-6 in the C rabbit group between days 3 and 7 (Interleukin-1β) and between days 3 and 28 (Interleukine-6) were relatively higher than the corresponding day 0 and control values. The decrease in the serum concentration of IL-10 (ng /mL) in B rabbit group from days 7 (36.96 ± 8.7) to 14 (128.12 ± 12.05) were significantly lower (P˂0.05) than the corresponding values in groups A and C rabbits. The values of Interleukine-10 in wound exudate of C rabbit group from days 7 (160.57 ± 23.76 ng /mL) to 21 (177.30 ± 8.60 ng /mL) were significantly higher (P<0.05) than the corresponding group D values. The evidence shows that, the values of Interleukin-1β and Interleukine-6 are up regulated in the inflammatory phase of wound healing in normoglycaemic and diabetic rabbits while the values of Interleukine-10 is down regulated during wound healing in diabetic rabbits. Therefore, the knowledge of interleukin markers shall be of significant roles in proffering solution for management of normoglycaemic and diabetic wounds.

Cytokine Profiles of Patients with Psoriasis Vulgaris who Experienced Acute Respiratory Infection with COVID-19

BACKGROUND: COVID-19, developing hyper-inflammatory reactions, can be a trigger factor for the manifestation or exacerbation of psoriasis in people who have undergone this infection. According to the scientific literature, patients with psoriasis are more likely to be infected with a coronavirus infection than the healthy population. However, they tolerate it in a milder form. At the same time, there have been reported exacerbation cases of the psoriatic process during the active phase of the disease and after experiencing COVID-19. AIM: The purpose of the study is to analyze the profiles of cytokines interleukin (IL)-17, IL-10, IL-8. IL-6, IL-4, and IL-1b in patients with psoriasis vulgaris and patients with psoriasis who contracted COVID-19. METHODS: We examined two groups of patients: The first group – 46 patients with psoriasis vulgaris in the period of exacerbation of the disease; the second group – 15 patients with exacerbation of psoriasis who contracted a mild or moderately severe coronavirus infection. The control group consisted of 15 conditionally healthy donors. The levels of cytokines IL-1b, IL-6, IL-8, IL-17a, IL-4, and IL-10 in the blood of patients and practically healthy individuals were determined by the enzyme immunoenzymatic method, using the “Human ELISE Kit” reagent sets (Fine Biotech., China), according to the manufacturer’s instructions. The difference between the study groups was assessed using the Mann–Whitney U-test. The results were considered significant at p < 0.01. All calculations were carried out using Microsoft Excel (Office 365). RESULTS: Psoriasis patients who have contracted COVID-19 had higher levels of IL-1b, IL-6, and IL-8 in their blood than patients with psoriasis vulgaris. CONCLUSION: Increased levels of IL-1β, IL-6, and IL-8 in the blood of patients with psoriasis may be a trigger factor for acute psoriasis in patients who have suffered from COVID-19.

Assessment of immune responses to a Comirnaty® booster following CoronaVac® vaccination in healthcare workers.

The immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunisation is variable. To describe the humoral immune response by correlating IgA and IgG antibodies with NAbs titration following CoronaVac® immunisation and an mRNA (Comirnaty®) booster among healthcare workers (HCWs) and to compare the cytokine and interleukin profiles between HCWs vaccinated with CoronaVac and coronavirus disease 2019 (COVID-19) infected patients. Samples from 133 HCWs collected at 20 (T1) and 90 (T2) days after CoronaVac immunisation and 15 (T3) days after a booster dose with the Comirnaty vaccine were analysed for IgA and IgG EIA and neutralisation assay. Cytokine levels from vaccinated individuals at T1 day and COVID-19 patients were compared. Neutralising antibodies (NAbs) were observed in 81.7% of participants at T1, but only 49.2% maintained detectable NAbs after 90 days. The booster dose increased NAbs response in all participants. The cytokines with the highest levels post-vaccination were IL-6 and MCP-1. The MCP-1, IL-18, and IFN- γ levels were higher in COVID-19 patients than in vaccinated HCWs, while IL-22 levels increased in the vaccinated HCWs group. The neutralisation titres in the T2 samples decreased, and antibody levels detected at T2 showed a more significant reduction than the neutralisation. The higher IL-22 expression in immunised individuals compared to those with COVID-19 suggests that IL-22 may be beneficial in protecting against severe disease.

Mitochondrial impairment related to the immunotoxicity of the herbicides clomazone, glyphosate and sulfentrazone in THP-1 cells.

Pesticides are indispensable for the cultivation of crops, especially those of economic importance, such as soybeans. Data on the annual use of herbicides in crops show that they correspond to 50%, making it the most used in agriculture. Therefore, the aim of this study was to evaluate the toxicity of the three commercial herbicides (clomazone, glyphosate, and sulfentrazone) in THP-1 cells. Cells were incubated with 0-5,000mg/L of the herbicides for 24h at 37°C for cytotoxicity evaluation. Additionally, a few toxicological pathways such as reactive species generation, mitochondrial impairment, and interleukin profile, which have been previously involved in the toxicity of pesticides, were also evaluated. A potential immunotoxic effect of the herbicides on THP-1 cells was observed, especially glyphosate, as it is a powerful agent of cellular immunotoxicity. It was also possible to verify an increase in oxidative stress and IL-8 levels and mitochondrial dysfunction. All herbicides showed cytotoxic effects in THP-1 monocytes, which were related to mitochondrial impairment.

Vitamin D Status Modestly Regulates NOD-Like Receptor Family with a Pyrin Domain 3 Inflammasome and Interleukin Profiles among Arab Adults.

Vitamin D (VD) deficiency has been associated with inflammation and dysregulation of the immune system. The NLRP3 inflammasome, a critical immune response component, plays a pivotal role in developing inflammatory diseases. VD hinders NLRP3 inflammasome activation and thus exerts anti-inflammatory effects. This study aimed to analyze the effect of VD deficiency on circulating levels of NLRP3 inflammasomes (NLRP3 and caspase-1) and associated interleukins (IL-1α, IL-1β, IL-18, IL-33 and IL-37) in Saudi adults. Methods: A total of 338 Saudi adults (128 males and 210 females) (mean age = 41.2 ± 9.1 years and mean BMI 31.2 ± 6.5 kg/m2) were included. Overnight-fasting serum samples were collected. Participants were stratified according to their VD status. Serum levels of NLRP3 inflammasomes and interleukins of interest were assessed using commercially available immuno-assays. Individuals with VD deficiency had significantly lower mean 25(OH)D levels than those with a normal VD status (29.3 nmol/L vs. 74.2 nmol/L, p < 0.001). The NLRP3 levels were higher in the VD-deficient group than their VD-sufficient counterparts (0.18 vs. 0.16, p = 0.01). Significant inverse associations were observed between NLRP3 levels with age (r = -0.20, p = 0.003) and BMI (r = -0.17, p = 0.01). Stepwise regression analysis identified insulin (β = 0.38, p = 0.005) and NLRP3 (β = -1.33, p = 0.03) as significant predictors of VD status, explaining 18.3% of the variance. The findings suggest that the VD status modestly regulates NLRP3 inflammasome and interleukin activities. This may provide novel insights into the pathogenesis and management of inflammatory disorders.

Interleukins in serum and bronchoalveolar lavage in patients with chronic obstructive pulmonary disease or bronchial asthma after pulmonary tuberculosis or pneumonia

The spread of respiratory diseases has become a topical issue of modern medicine. The prevalence of the diseases caused the rising rates of disability and mortality among people affected by respiratory diseases. The clinical course of respiratory diseases includes the disorders of general and local adaptive and protective mechanisms and cell-mediated connections. Objective — to determine the interleukin profile of serum and bronchoalveolar lavage for the verification of chronic obstructive pulmonary disease (COPD) or bronchial asthma in patients with pulmonary tuberculosis or pneumonia with bronchial obstruction syndrome. Materials and methods. 67 patients affected by chronic obstructive pulmonary disease and 33 patients diagnosed with bronchial asthma who were hospitalized in the Pulmonology Lviv Regional Diagnostic Center during 2015—2020, were examined. The patients were verified with a non-complicated tuberculosis without any destructive changes evident in the lungs (the first or third clinical category of patients), the community-acquired pneumonia with the bronchial obstruction syndrome. Pro-inflammatory interleukins IL-1β, IL-2, IL-6, TNF-α and anti-inflammatory IL-4 in serum and bronchoalveolar lavage were revealed during the lobar and tertiary bronchi fiber-optic bronchoscopy. Results and discussion. The interleukins misbalance was evident: the decrease in IL-1β and IL-2 and the increase in IL-6 and TNF-α by 4.5 times as compared to the unaffected donors was revealed in the patients with chronic obstructive pulmonary disease. The significant decrease in IL-4 was revealed pointing at the high probability of the severe and prolonged COPD and leading to frequent exacerbation and compilations of the disease. By contrast, the patients diagnosed with bronchial asthma showed higher IL-1β and IL-2 as compared to the unaffected patients; the level of IL-6 was higher as compared to the COPD patients, while TNF-α was lower. The patients with bronchial asthma showed higher IL-4 than the unaffected donors and the patients with COPD. Conclusions. The intensity of interleukins expression (especially pro-inflammatory) revealed the level of inflammation based on the acute-phase proteins in the proteolytic-antiproteolytic balance, which may be also used as the additional criteria for the differential diagnostics and justification for the treatment optimization.

Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation-Is There Room for Interleukin Profiles?

The current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic tool in children suspected to have TCMR. A total of n = 53 blood samples obtained on the day of or up to 3 days before liver biopsy performed for suspected TCMR at median 18 days (range 7-427) after pLT in n = 50 children (38% female, age at pLT 1.8 (0.5-17.5) years) were analysed for circulating cytokine levels using Luminex-based Multiplex technology. Diagnostic accuracy of cytokine concentrations was assessed using a multivariable model based on elastic net regression and gradient boosting machine analysis. TCMR was present in 68% of biopsies. There was strong evidence that patients with TCMR had increased levels of soluble CXCL8, CXCL9, CXCL10, IL-16, IL-18, HGF, CCL4, MIF, SCGF-β, and HGF before biopsy. There was some evidence for increased levels of sCD25, ICAM-1, IL-6, IL-3, and CCL11. Diagnostic value of both single cytokine levels and a combination of cytokines and clinical markers was poor, with AUROCs not exceeding 0.7. Patients with TCMR showed raised levels of cytokines and chemokines reflective of T-cell activation and chemotaxis. Despite giving insight into the mechanisms of TCMR, the diagnostic value of soluble cytokines for the confirmation of TCMR in a clinical scenario of suspected TCMR is poor.

Evaluation of blood interleukin levels and their correlations in the patients with diabetic retinopathy with mild and moderate cognitive impairment

Systemic immunological disorders are associated with various geriatric conditions, including cognitive dysfunction. However, in patients with diabetic retinopathy, the changes of blood interleukin profile were studied without considering the severity of cognitive impairment. The aim of this study was to analyze blood plasma levels and intercorrelations of interleukins in the patients with diabetic retinopathy accompanied by mild and moderate cognitive impairment. Fifty-four elderly patients with diabetic retinopathy and mild cognitive impairment, and 62 patients with diabetic retinopathy and moderate cognitive disorders underwent inpatient examination and treatment at the Tambov branch of the S. Fedorov Center of Eye Microsurgery over 2021-2022. The interleukins contents in blood plasma were studied by enzyme immunoassay using the Protein Contour kit, including IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-17, IL-18. The diagnostics of diabetic retinopathy was based on comprehensive ophthalmological examination, according to the Clinical recommendations of the Society of the Russian Association of Ophthalmologists «Diabetes mellitus: diabetic retinopathy, diabetic macular edema». Cognitive functions were assessed according to a valid Mini- Mental-State-Examination scale. It has been shown that the patients with diabetic retinopathy and moderate cognitive impairment have a significantly increased level of all the studied proinflammatory interleukins, as compared to similar cohort with diabetic retinopathy accompanied by a mild cognitive impairment. In mild cognitive disorders, the content of IL-6 in blood plasma was higher (24.4±2.1 pg/mL versus 5.1±0.8 pg/mL, p &lt; 0.001). Development of moderate cognitive impairment in the patients with diabetic retinopathy was also accompanied by a statistically significant increase of plasma IL-8 to 36.7±3.5 pg/mL versus 10.5±2.3 pg/mL with mild cognitive impairment; IL-17, to 21.9±1.8 pg/mL versus 8.5±1.1 pg/mL, respectively. Concentrations of anti-inflammatory interleukins in blood plasma of the patients with diabetic retinopathy and moderate cognitive dysfunction were significantly decreased, i.e., IL-4 to 2.1±0.3 pg/mL versus 3.4±0.5 pg/mL in cases of mild mental deterioration; IL-10, to 8.7±0.5 pg/mL versus 15.4±1.3 pg/mL, respectively. A sufficient correlation was shown between the levels of systemic interleukins and moderate cognitive disorders in the patients with diabetic retinopathy. For the proinflammatory interleukins in cases of moderate cognitive impairment, an inverse correlations with IL-1β (r = -0.336; p = 0.021), IL-6 (r = -0.584; p = 0.019), IL-8 (r = -0.469; p = 0.006), and with IL-17 (r = -0.348; p = 0.018) were shown. The content of IL-4 and IL-10 in blood plasma of the patients with diabetic retinopathy correlated with moderate cognitive impairment at a significant level of r = +0,407 (p = 0.016) and r = +0.359 (p = 0.008), respectively. In mild cognitive impairment, the correlations with fewer numbers of interleukins were revealed, i.e., IL-1β, IL-6, IL-8 and IL-10, and exhibit weaker connections, except of IL-6 (a moderate connection level). Development of moderate cognitive impairment among the patients with diabetic retinopathy may be caused by increase in IL-1β, IL-6, IL-8, IL-17, and a decrease in IL-10.

Immunoglobulin use in childhood epilepsy

Background: Epilepsy's aetiology is well-known to include an immune component. Several clinical and laboratory research have discovered abnormalities in epileptic patients' immune system branches when compared to the general population. Such anomalies include immunoglobulin deficiencies (mainly immunoglobulin A and immunoglobulin G2), an increased prevalence of specific human leukocyte antigen types, and alterations in cytokine and interleukin profiles. In people with epilepsy, autoantibodies were discovered against glutamic acid decarboxylase, components of the voltage-gated potassium channel complex, and the N-methyl-D-aspartate, gamma-aminobutyric acid, a-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid, and glutamate receptor three receptors. Immune modulating drugs like corticosteroids and corticotrophin have also been demonstrated to help with seizures. In view of these findings, immunosuppressive medicine has potential as an add-on therapy for refractory epilepsy. Aim: We aimed to evaluate the efficacy of immunoglobulin in childhood epilepsy. Conclusion: Despite the fact that new medications are constantly being developed to treat intractable infantile epilepsy, the refractory rate remains high. Despite several investigations on the subject, predictive variables for a good intravenous immunoglobulin response have yet to be identified. In some epileptic disorders, such as idiopathic West syndrome and electrical status epilepticus during sleep, intravenous immunoglobulin appears to be beneficial.

Three Component Composite Scaffolds Based on PCL, Hydroxyapatite, and L-Lysine Obtained in TIPS-SL: Bioactive Material for Bone Tissue Engineering

In this research, we describe the properties of three-component composite foam scaffolds based on poly(ε-caprolactone) (PCL) as a matrix and hydroxyapatite whiskers (HAP) and L-Lysine as fillers (PCL/HAP/Lys with wt% ratio 50/48/2). The scaffolds were prepared using a thermally induced phase separation technique supported by salt leaching (TIPS-SL). All materials were precisely characterized: porosity, density, water uptake, wettability, DSC, and TGA measurements and compression tests were carried out. The microstructure of the obtained scaffolds was analyzed via SEM. It was found that the PCL/HAP/Lys scaffold has a 45% higher Young’s modulus and better wettability compared to the PCL/HAP system. At the same time, the porosity of the system was ~90%. The osteoblast hFOB 1.19 cell response was also investigated in osteogenic conditions (39 °C) and the cytokine release profile of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was determined. Modification of PCL scaffolds with HAP and L-Lysine significantly improved the proliferation of pre-osteoblasts cultured on such materials.

Simulated Microgravity Affects the TNF-α-Induced Interleukin Profile of Endothelial Cells Depending on the Initial ICAM-1 Expression

Simulated Microgravity Affects the TNF-α-Induced Interleukin Profile of Endothelial Cells Depending on the Initial ICAM-1 Expression

Comparison of FOXP3 and Interleukin 35 Expression Profiles in Kidney Transplant Recipients With Excellent Long-Term Graft Function and Acute Rejection

Transplant tolerance is defined as graft acceptance without long-term use of immunosuppressive agents. Regulatory T cells are involved in the maintenance of peripheral self-tolerance by actively suppressing the activation and expansion of autoreactive T cells. In the present study, we compared the expression profiles of forkhead box protein P3 (FOXP3) and interleukin 35 in kidney transplant recipients who had excellent long-term graft function under immunosuppression versus recipients who had acute rejection. The 40 kidney transplant recipients included in this study were divided into 2 groups: 27 recipients with excellent long-term graft function and 13 recipients with acute rejection. After collection of whole peripheral blood, peripheral blood mononuclear cells were isolated from the blood samples. After RNAextraction and cDNAsynthesis from each collected sample, expression levels of interleukin 35 and FOXP3 were determined using in-house SYBER green-based real-time polymerase chain reaction. We used t tests to analyze data. Mean ages of recipients with excellent longterm graft function and recipients with acute rejection were 42.1 and 45.5 years, respectively. We found that FOXP3 and interleukin 35 expression levels were significantly increased in recipients with excellentlongterm graftfunction comparedwith recipientswith acute rejection. FOXP3 expression levels were significantly higher in those with excellent long-term graft function with graft survivalrate of <10 years,whereas interleukin 35 expression levels were significantly higher in patients with graft survival rate >10 years (P < .05). Expression levels of FOXP3 and interleukin 35 were greater in those from 35 to 50 years old versus with those in the other age ranges. Expression patterns of FOXP3 and interleukin 35 may have the potential to be used as prognostic biomarkers for kidney transplant outcomes.

Enhancing the Pharmacokinetic Profile of Interleukin 2 through Site-Specific Conjugation to a Selective Small-Molecule Transthyretin Ligand.

Protein drugs hold great promise as therapeutics for a wide range of diseases. Unfortunately, one of the greatest challenges to be addressed during clinical development of protein therapeutics is their short circulation half-life. Several protein conjugation strategies have been developed for half-life extension. However, these strategies have limitations and there remains room for improvement. Here, we report a novel nature-inspired strategy for enhancing the in vivo half-life of proteins. Our strategy involves conjugating proteins to a hydrophilic small molecule that binds reversibly to the plasma protein, transthyretin. We show here that our strategy is effective in enhancing the pharmacokinetic and pharmacodynamic properties of human interleukin 2 in rats, potentially opening the door for more effective and safer cancer immunotherapies. To our knowledge, this is the first example of successful use of a small-molecule that not only extends the half-life but also maintains the smaller size, binding potency, and hydrophilicity of proteins.