Association Of Pro-inflammatory Cytokines Research Articles

Association of pro-inflammatory cytokines, adipokines and hepatokine with incident diabetes in India: a nested case-control study within CARRS cohort.

To study the association of pro-inflammatory markers with incident diabetes in India. We did a nested case-control study within the CARRS (Centre for ArdiometabolicRiskReduction inSouth Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use. Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI:1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI:1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI:0.06, 0.55]). Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians.

Association of pro-inflammatory cytokines with trauma and post-traumatic stress disorder visiting a tertiary care hospital in Kathmandu.

Post-traumatic stress disorder (PTSD) is a mental disorder that can occur after trauma. Although inflammatory markers such as cytokines are found altered in trauma and PTSD, there is no consensus regarding which can be considered as biomarkers. Studies from South Asia region is also rare. We studied cytokines among trauma affected patients and matched healthy controls. Fifty patients (cases) with trauma, visiting the University hospital in Kathmandu and thirty-nine healthy controls were selected, and the levels of cytokines were determined using a Luminex IS 200. We compared the levels of the cytokines in thirty-four age and gender matched pairs of case and control among three groups: healthy volunteers, cases diagnosed as PTSD, and cases without PTSD. Among the 34 pair-matched cases and controls, IL-6 was significantly higher in both PTSD positive cases [2.43 (0.00-14.54) pg/ml; p = 0.004] and PTSD negative cases [3.00 (0.92-3.86) pg/ml; p = 0.005], than in controls [0.39 (0.00-11.38) pg/ml]. IL-1β was significantly higher in PTSD positive cases [0.17 (0.00-5.27) pg/ml; p = 0.011] than in controls 0.00 (0.00-0.12) pg/ml. Other cytokines did not show significant differences. IL-6 was higher in both the trauma affected groups and IL-1β was higher in the trauma affected group with PTSD when compared to healthy controls. This supports the immune system activation hypothesis after trauma.

Association of pro-inflammatory cytokines, inflammatory proteins with atherosclerosis index in obese male subjects.

Investigation the association of pro-inflammatory markers interleukin (IL)-1β and IL- 10 expression, serum levels of C-reactive protein (CRP), cyclooxygenase-2 (COX2), High-density lipoprotein (HDL), Apolipoprotein A1 (ApoA1), and ATP Binding Cassette Subfamily A Member 1 (ABCA1) inflammatory proteins with atherosclerosis index (homocysteine) in normal-weight and obese male subjects. 59 males including 30 obese (Body mass index (BMI) of≥30kg/m2) and 29 normal-weight (BMI of 18.5-24.9kg/m2) were joined to this study. Plasma levels of IL-1β and IL-10 (pg/mL), CRP (pg/mL), COX-2 (ng/mL), APOA1 (mg/dL), ABCA1 (ng/mL), HDL, Cholesterol, and Triglyceride (TG) (mg/dL), and homocysteine (µmol/L) was measured. Association of these biomarkers with homocysteine was determined. Obese subjects had higher serum levels of IL10, IL1β, CRP, COX-2, TG, and cholesterol concentrations (allp<0.05 except IL-10 and cholesterol) and low levels of HDL, APOA1, and ABCA1 (non-significant differences) in comparison to normal-weight group. Homocysteine levels were high in obese men with no significant differences between the two groups. In obese subjects, homocysteine had a significant inverse correlation with APOA1, ABCA1, and HDL, and a strong and moderate positive correlation was found with CRP and TG levels, respectively. High level of homocysteine and its correlation with inflammation proteins and markers in obese subjects appear to be contributed with atherosclerosis development.

Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions.

Despite successful endovascular therapy, a proportion of stroke patients exhibit long-term functional decline, regardless of the cortical reperfusion. Our objective was to evaluate the early activation of the adaptive immune response and its impact on neurological recovery in patients with large vessel occlusion (LVO). Nineteen (13 females, 6 males) patients with acute LVO were enrolled in a single-arm prospective cohort study. During endovascular therapy (EVT), blood samples were collected from pre and post-occlusion, distal femoral artery, and median cubital vein (controls). Cytokines, chemokines,cellular and functional profiles were evaluated with immediate and follow-up clinical and radiographic parameters, including cognitive performance and functional recovery. In the hyperacute phase (within hours), adaptive immune activation was observed in the post-occlusion intra-arterial environment (post). Ischemic vascular tissue had a significant increase in T-cell-related cytokines, including IFN-γ and MMP-9, while GM-CSF, IL-17, TNF-α, IL-6, MIP-1a, and MIP-1b were decreased. Cellularity analysis revealed an increase in inflammatory IL-17+ and GM-CSF+ helper T-cells, while natural killer (NK), monocytes and B-cells were decreased. A correlation was observed between hypoperfused tissue, infarct volume, inflammatory helper, and cytotoxic T-cells. Moreover, helper and cytotoxic T-cells were also significantly increased in patients with improved motor function at 3 months. We provide evidence of the activation of the inflammatory adaptive immune response during the hyperacute phase and the association of pro-inflammatory cytokines with greater ischemic tissue and worsening recovery after successful reperfusion. Further characterization of these immune pathways is warranted to test selective immunomodulators during the early stages of stroke rehabilitation.

MO635PRO-INFLAMMATORY CYTOKINES IL-6 AND IL-17 DISPLAY A PARTICULAR MOLECULAR PATTERN IN ASSOCIATION WITH DYSREGULATED MIRNAS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN THE EARLY STAGES OF DIABETIC KIDNEY DISEASE

Abstract Background and Aims Glomerular injury and proximal tubule (PT) dysfunction have intricate mechanisms in diabetic kidney disease (DKD). Pro-inflammatory cytokines are involved in the initiation and progression of DKD through mediating the inflammatory response, both at glomerular and proximal tubular level. miRNAs are able to modulate cellular and biochemical functions, thus intervening in the pathogenesis of DKD. The aim of the study, performed on patients with type 2 diabetes mellitus (DM), was to evaluate selective pro-inflammatory cytokines in relation to biomarkers of podocyte lesion and of PT dysfunction. Particular molecular pathways, such as specific miRNA profiles operating in this relation, have also been studied. Method A number of 126 patients with type 2 DM, staged by albuminuria [39 normoalbuminuric – urinary albumin/creatinine ratio UACR)&amp;lt;30mg/g; 45 microalbuminuric–UACR-30–300mg/g; 42 macroalbuminuric–UACR&amp;gt;300mg/g], and 23 healthy control subjects were included in a cross-sectional study. All patients were evaluated concerning biomarkers of podocyte injury (nephrin, podocalyxin, synaptopodin) and of PT dysfunction [Kidney injury molecule-1(KIM-1), N-acetyl-beta-D-glucuronidase (NAG), alpha 1- microglobulin]. Also, serum and urinary levels of specific interleukins (IL-6, IL-17), serum cystatin C, and eGFR were determined. Serum and urinary miRNAs (miRNA-21, miRNA-124, miRNA-146a, miRNA-192) were assessed by RT-PCR. Results The biomarkers of podocyte lesion and of PT dysfunction were increased, even in normoalbuminuric type 2 DM patients. Serum and urinary IL-6 and IL-17 showed increased levels in type 2 DM patients, across all groups studied. The model provided by univariable regression analysis showed that IL-6 and IL-17 correlated directly with biomarkers of podocyte injury (nephrin, podocalyxin, synaptopodin), of PT dysfunction (KIM-1, NAG, alpha 1-microglobulin), as well as with UACR. Negative correlations have been identified regarding eGFR. In multivariable regression analysis, serum IL-6 correlated directly with synaptopodin, NAG, and negatively with eGFR (p&amp;lt;0.00001, R2=0.805); serum IL-17 correlated directly with synaptopodin, NAG, KIM-1, UACR, and negatively with eGFR (p&amp;lt;0.00001, R2=0.941); urinary IL-6 correlated directly with synaptopodin, NAG, and negatively with eGFR (p&amp;lt;0.00001, R2=0.889); urinary IL-17 correlated directly with synaptopodin, nephrin, NAG, and negatively with eGFR (p&amp;lt;0.00001, R2=0.905). Also, important associations were found between specific interleukins and miRNAs. In univariable regression analysis, IL-6 and IL-17 correlated directly with miRNA-21 and miRNA-124, and negatively with miRNA-146a and miRNA-192. The models provided by multivariable regression analysis showed that urinary IL-6 correlated directly with urinary miRNA-21, and negatively with urinary miRNA-192 (p&amp;lt;0.00001, R2=0.886). Urinary IL-17 displayed direct correlations with urinary miRNA-21, and negative correlations with urinary miRNA-192 (p&amp;lt;0.00001, R2=0.860). Serum IL-6 correlated directly with serum miRNA-21, miRNA-124, and indirectly with serum miRNA-146a, miRNA-192 (p&amp;lt;0.00001, R2=0.862). Serum IL-17 showed direct correlations with serum miRNA-21, miRNA-124, and negative correlations with serum miRNA-192 (p&amp;lt;0.00001, R2=0.745). Conclusion In the early stages of DKD, there is an association of pro-inflammatory cytokines with specific miRNAs, and with biomarkers of podocyte injury and of PT dysfunction. IL-6 and IL-17, as well as dysregulated miRNA-21, miRNA-124, miRNA-146a, and miRNA-192 display a particular molecular pattern, in relation to complex mechanisms that can initiate and maintain the chronic inflammatory response in DKD. Routine detection of these interleukins may provide biomarkers to refine the diagnosis of early renal involvement in the course of type 2 DM, independently of albuminuria and level of renal function.

Association of pro-inflammatory cytokines with clinical features in euthymic patients with Bipolar-I-Disorder

BackgroundA chronic low-grade inflammatory state appears to be a relevant mechanism in the pathophysiology of bipolar disorder. Pro-inflammatory cytokines may influence disease course and individual symptomatology; and biological markers correlating with illness features may be of utility in clinical decision making during euthymia. Methods51 euthymic outpatients with Bipolar-I-Disorder (BD-I) and 93 healthy controls (HC) were investigated. Comparisons between groups, and correlations with clinical features were performed. Serum concentrations of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and soluble interleukin-6 receptor (sIL-6R) were evaluated by ELISA under highly standardized conditions. Clinical features included duration of illness, number of previous suicide attempts and mood episodes (manic, hypomanic, depressive), scores of the Young Mania Rating Scale (YMRS), the Inventory of Depressive Symptoms (IDS-30), the Pittsburg Sleep Quality Index (PSQI), and the Global Assessment of Functioning (GAF). ResultsNo significant difference in serum concentrations of IL-1β, TNF-α, and sIL-6R between BD-I euthymic patients and HC could be identified. Among euthymic BD-I patients, a positive correlation of rs = 0.47 (p = 0.004) between levels of IL-1β and IDS-30 score was identified. LimitationsThe design was cross-sectional, most patients were receiving medication, only 3 cytokines were assessed, only euthymic BD-I patients were evaluated. ConclusionsThe findings suggest that elevated pro-inflammatory cytokine concentrations are likely state rather than trait markers of BD-I. It also seems unlikely that cytokine concentrations are clinically informative interepisode. An inflammatory component might possibly be involved in the pathophysiology of subsyndromic depression in BD-I, and conceivably of bipolar depression per se.

Chronically reduced IL-10 plasma levels are associated with hippocampal sclerosis in temporal lobe epilepsy patients

BackgroundIncreasing evidence supports the role of soluble inflammatory mediators in the pathogenesis of refractory temporal lobe epilepsy (TLE). Hippocampal sclerosis (HS) is a well-described pathohistological abnormality in TLE. The association of proinflammatory cytokines with epileptic disease profiles is well established; however, the potential significance of circulating interleukin 10 (IL-10), particularly in TLE-associated HS, is still poorly understood. Therefore, taking into consideration the neuroprotective and anticonvulsive effects of IL-10, we performed this study to examine the role of the plasma levels of IL-10 in patients with TLE with HS (TLE + HS), TLE without HS (TLE-HS) and with other types of epilepsy.MethodsThis study included 270 patients with refractory epilepsy who were classified into four groups: i) 34 patients with TLE + HS, ii) 105 patients with TLE-HS, iii) 95 patients with extra-TLE (XLE) and iv) 36 patients with idiopathic generalized epilepsy (IGE). The plasma IL-10 levels were quantified using a commercially available enzyme-linked immunosorbent assay (ELISA).ResultsIL-10 levels were significantly lower in TLE + HS than in TLE-HS (p = 0.013). In a subgroup of TLE-HS patients who had seizures 1 month before sampling, patients with seizures had significantly higher IL-10 levels than patients who were seizure-free (p = 0.039). Among a small group (n = 15) of non-refractory TLE-HS patients, IL-10 levels showed a moderate negative correlation with the duration of epilepsy (r = − 0.585, p = 0.023).ConclusionsThis study demonstrated that chronically reduced levels of plasma IL-10 were associated with HS in TLE patients, suggesting that there was an inadequate systemic anti-inflammatory immune response. These results could provide new biological insights into the pathophysiology of HS in TLE. We also found that the production of IL-10 could be affected by the seizure frequency and declined concomitantly with increased disease durations. Therefore, the measurement of plasma IL-10 may have diagnostic value as a biomarker for stratifying TLE + HS from other epilepsy types or as a marker of disease progression towards a progressive form of epilepsy.

Interleukin in endometriosis-associated infertility-pelvic pain: systematic review and meta-analysis.

The objective is to study the significance of altered interleukin levels in endometriosis-related infertility or pelvic pain. The present systematic review and meta-analysis includes a discussion on the roles of interleukin in the physiopathology of endometriosis-associated infertility and/or pelvic pain. We included all studies in which interleukins in peritoneal fluid, follicular fluid or serum from patients were measured and that correlated the findings with either peritoneal or deep endometriosis-associated infertility or pelvic pain. For the meta-analysis, we selected studies on the following cytokines: interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8). Endometriosis is a chronic inflammatory disease. Inflammatory processes clearly participate in the etiology of endometriosis. Cytokines are mediators of inflammation, and increase in their concentration in plasma or other body fluids signals the presence and extent of tissue lesions. A number of studies have reported on the association between higher cytokine levels and progression or maintenance of endometriosis and coexisting infertility or pelvic pain. The results of the analyses support that an association exists between elevated serum IL-6 and/or IL-8 concentrations and the occurrence of endometriosis-associated infertility. Such association was not found for endometriosis-associated pain. In spite of accumulated evidence on the association of pro-inflammatory cytokines and endometriosis, it still is not clear if and how these mediators participate in the physiopathology of endometriosis-associated infertility or pelvic pain, in part due to poor quality of the evidence established in the vast majority of interleukins and challenges in endometriosis research reproducibility. In summary, the results of the analyses support that an association exists between elevated serum IL-6 and/or IL-8 concentrations and the occurrence of endometriosis-associated infertility.

Association of pro-inflammatory cytokines and monocyte subtypes in older and younger patients on clinical outcomes after mechanical circulatory support device implantation

Noninvasive immunologic analysis of peripheral blood holds promise for explaining the mechanism of development of adverse clinical outcomes, and may also become a method for patient risk stratification before or after mechanical circulatory support device (MCSD) implantation. Dysregulation of the innate immune system is associated with increased patient age but has yet to be evaluated in the older patient with advanced heart failure undergoing MCSD surgery.Patients pre- and post-MCSD implantation had peripheral blood mononuclear cells (PBMC) and serum isolated. Multiparameter flow cytometry was used to analyze markers of innate cell function, including monocyte subtypes. Multiplex cytokine analysis was performed. MELD-XI and SOFA scores were utilized as surrogate markers of outcomes.Increased levels of pro-inflammatory cytokines including IL-15, TNF-α, and IL-10 were associated with increased MELD-XI and SOFA scores. IL-8, TNF- α, and IL-10 were associated with risk of death after MCSD implantation, even with correction for patient age. Increased frequency of ‘classical’ monocytes (CD14 + CD16−) were associated with increased MELD-XI and SOFA scores.This suggests that inflammation and innate immune system activation contribute to progression to multiorgan system failure and death after MCSD surgery. Development of noninvasive monitoring of peripheral blood holds promise for biomarker development for candidate selection and patient risk stratification.

Association of Pro-inflammatory cytokines and Benign Thyroid nodules: A prospective case-control study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Association of Pro-inflammatory Cytokines with the Psychological Problems in Children with Sickle Cell Disease

Association of Pro-inflammatory Cytokines with the Psychological Problems in Children with Sickle Cell Disease

P.4.c.010 - Association of pro-inflammatory cytokines with serum levels of fatty acid in patients with PTSD − a cohort study

P.4.c.010 - Association of pro-inflammatory cytokines with serum levels of fatty acid in patients with PTSD − a cohort study

PM352. Association of pro-inflammatory cytokines with tic disorders in children and adolescents

PM352. Association of pro-inflammatory cytokines with tic disorders in children and adolescents

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study

Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. Chemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). While elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Association of pro-inflammatory cytokines, cortisol and depression in patients with chronic obstructive pulmonary disease.

Evidence suggests that pro-inflammatory cytokines and cortisol play a crucial role in the etiology of chronic obstructive pulmonary disease (COPD) and depression. Depression occurs commonly among COPD patients and an earlier diagnosis would be beneficial. This study investigated the associations between depression, sputum cytokines and salivary cortisol in COPD patients. The diurnal rhythms of sputum IL-1, IL-6, TNF-α and salivary cortisol were measured in COPD patients with depression compared to those only with depression, or COPD and healthy controls. The area under the diurnal variation curves (AUC) over the 24h time course and relative diurnal variation (VAR) were calculated while correlation and regression analysis were performed. Patients with co-morbid depression and COPD showed an increasing sputum IL-1, sputum TNF-α AUC and a decreasing salivary cortisol VAR (P<0.001). The combination of sputum TNF-α AUC, sputum IL-1 AUC, sputum IL-6 AUC and salivary cortisol VAR performed best as a potential biomarker in the diagnosis of depression in COPD patients, with a sensitivity of 94.74% and a specificity of 96.67%. Positive correlations were found between sputum IL-1 AUC and sputum TNF-α AUC versus depressive symptoms, respectively a negative correlation was found between salivary cortisol VAR and depression. They were independently associated with depression in logistic regression models. Depression in COPD is associated with higher 24-h overall levels of sputum IL-1, TNF-α and flattened diurnal salivary cortisol. These non-invasive sputum and salivary biomarkers may serve as a simple clinical tool for the early diagnosis of depression in COPD patients.

Association of proinflammatory cytokines and islet resident leucocytes with islet dysfunction in type 2 diabetes.

Chronic inflammation in type 2 diabetes is proposed to affect islets as well as insulin target organs. However, the nature of islet inflammation and its effects on islet function in type 2 diabetes remain unclear. Moreover, the immune cell profiles of human islets in healthy and type 2 diabetic conditions are undefined. We aimed to investigate the correlation between proinflammatory cytokine expression, islet leucocyte composition and insulin secretion in type 2 diabetic human islets. Human islets from organ donors with or without type 2 diabetes were studied. First and second phases of glucose-stimulated insulin secretion were determined by perifusion. The expression of inflammatory markers was obtained by quantitative PCR. Immune cells within human islets were analysed by FACS. Type 2 diabetic islets, especially those without first-phase insulin secretion, displayed higher CCL2 and TNFa expression than healthy islets. CD45(+) leucocytes were elevated in type 2 diabetic islets, to a greater extent in moderately functional type 2 diabetic islets compared with poorly functional ones, and corresponded with elevated ALOX12 but not with CCL2 or TNFa expression. T and B lymphocytes and CD11c(+) cells were detectable within both non-diabetic and type 2 diabetic islet leucocytes. Importantly, the proportion of B cells was significantly elevated within type 2 diabetic islets. Elevated total islet leucocyte content and proinflammatory mediators correlated with islet dysfunction, suggesting that heterogeneous insulitis occurs during the development of islet dysfunction in type 2 diabetes. In addition, the altered B cell content highlights a potential role for the adaptive immune response in islet dysfunction.

Regulation of CYP27B1 and CYP24A1 gene expression by recombinant pro-inflammatory cytokines in cultured human trophoblasts

Placenta is an important source of endocrine and immunological factors. During pregnancy, calcitriol, the active metabolite of vitamin D, is also metabolized by decidua and placental tissue by means of CYP27B1 and CYP24A1 for synthesis and inactivation of calcitriol respectively. Calcitriol production is regulated by several factors in a tissue-specific manner. However, the association of pro-inflammatory cytokines on calcitriol metabolism has not been studied in human placenta. The aim of the present study was to investigate the effects of TNF-α, INF-γ, IL-6 and IL-1β upon CYP27B1 and CYP24A1 gene expression in primary cultures of human placental cells. Placentas were obtained immediately after delivery by cesarean section from normotensive women. Cytokine effects upon mRNA of CYPs in enriched trophoblastic cell preparations were evaluated by using qPCR. The results showed that incubation of trophoblasts in the presence of each cytokine resulted in a significant increase of both CYPs expression. Interestingly, TNF-α increased significantly the ratio of CYP24A1/CYP27B1 gene expression, while IFN-γ preferentially induced CYP27B1, whereas IL-1β and IL-6 stimulated gene expression of both CYPs in the same proportion. The results suggest that cytokines among other factors regulate calcitriol metabolism in human placenta; specifically, INF-γ may contribute to calcitriol production while TNF-α favors its catabolism.

Association of Pro-Inflammatory Cytokines and Iron Regulatory Protein 2 (IRP2) with Leishmania Burden in Canine Visceral Leishmaniasis

Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

Type 2 diabetes mellitus is a major risk factor for the development of active tuberculosis, although the biological basis underlying this susceptibility remains poorly characterized. To identify the influence of coincident diabetes mellitus on cytokine levels in pulmonary tuberculosis, we examined circulating levels of a panel of cytokines and chemokines in the plasma of individuals with tuberculosis with diabetes and compared them with those of individuals without diabetes. Tuberculosis with diabetes is characterized by elevated circulating levels of type 1 (IFN-γ, tumor necrosis factor-α, and IL-2), type 2 (IL-5), and type 17 (IL-17A) cytokines but decreased circulating levels of IL-22. This was associated with increased systemic levels of other proinflammatory cytokines (IL-1β, IL-6, and IL-18) and an antiinflammatory cytokine (IL-10) but not type 1 IFNs. Moreover, tuberculosis antigen-stimulated whole blood also showed increased levels of proinflammatory cytokines. Finally, type 1 and type 17 cytokines in plasma exhibit a significant positive correlation with hemoglobin A1C levels, indicating that impaired control of diabetes is associated with this proinflammatory milieu. Multivariate analysis revealed that the association of proinflammatory cytokines with diabetes mellitus was not influenced by age, sex, or other metabolic parameters. Our data reveal that tuberculosis with diabetes is characterized by heightened cytokine responsiveness, indicating that chronic inflammation underlying type 2 diabetes potentially contributes to increased immune pathology and poor control in tuberculosis infection.

Association of pro-inflammatory cytokines and T-cell activation marker with CA-125 levels in obese patients with heart failure: Implications for complex immunoinflammatory pathophysiology

Association of pro-inflammatory cytokines and T-cell activation marker with CA-125 levels in obese patients with heart failure: Implications for complex immunoinflammatory pathophysiology