scholarly journals Serum levels of inhibitory costimulatory molecules and correlations with levels of innate immune cytokines in patients with pulmonary tuberculosis

2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110368
Author(s):  
Yunjuan Zhao ◽  
Jia Zhang ◽  
Bing Xue ◽  
Fengbo Zhang ◽  
Qian Xu ◽  
...  

Objective To analyze serum levels of inhibitory costimulatory molecules and their correlations with innate immune cytokine levels in patients with pulmonary tuberculosis (PTB). Methods Data for 280 PTB patients and 280 healthy individuals were collected. Serum levels of immune molecules were measured using ELISA. Univariate, multivariate, subgroup, matrix correlation, and receiver operating characteristic curve analyses were performed. Results Host, environment, lifestyle, clinical features, and medical history all influenced PTB. Serum levels of soluble programmed death ligand 1 (sPD-L1), soluble T-cell immunoglobulin- and mucin-domain–containing molecule 3 (sTim-3), soluble galectin-9 (sGal-9), interleukin (IL)-4, and IL-33 were significantly higher in patients with PTB, while levels of IL-12, IL-23, IL-18, and interferon (IFN)-γ were significantly lower. Serum levels of sTim-3 were higher in alcohol users. Levels of sTim-3 were negatively correlated with those of IL-12. Levels of IL-12, IL-23, and IL-18 were positively correlated with those of IFN-γ, while levels of IL-12 were negatively correlated with those of IL-4. The areas under the curve of sPD-L1, sTim-3, sGal-9, IL-12, IL-23, IL-18, IFN-γ, IL-4, and IL-33 for identifying PTB were all >0.77. Conclusions Inhibitory costimulatory molecules may be targets for controlling PTB. Immune molecules may be helpful for diagnosis of PTB.

2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis


2013 ◽  
Vol 39 (6) ◽  
pp. 719-727 ◽  
Author(s):  
Beatriz Lima Alezio Muller ◽  
Daniela Maria de Paula Ramalho ◽  
Paula Fernanda Gonçalves dos Santos ◽  
Eliene Denites Duarte Mesquita ◽  
Afranio Lineu Kritski ◽  
...  

OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis.METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts.RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels.CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment.


2018 ◽  
Vol 17 (8) ◽  
pp. 618-625 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Sadiq Neama Al-Kufi ◽  
Arafat Hussein Al-Dujaili ◽  
Michael Maes

Background & Objective: Major depressive disorder (MDD) has been associated with inflammatory processes, including increased cytokine levels, even in individuals who are otherwise physically healthy, while some MDD patients may show insulin resistance (IR). Method: However, correlations between cytokines and IR parameters have not been studied extensively in MDD. In the present study, we measured IL-1β, IL-4, IFN-γ, TGF-β1, insulin and glucose in 63 MDD patients and 27 healthy controls. The associations between cytokine levels and IR were examined. Results: The results revealed a significant increase (p<0.05) in serum levels of IL-1β, IL-4, IFN-γ, TGF-β1, insulin, insulin/glucose ratio, and insulin resistance (HOMA2IR) in MDD patients as compared with controls. There was a significant correlation between HOMA2IR with both IFN-γ (ρ=0.289, p<0.05) and TGF-β1 (ρ=0.364, p<0.05). Conclusion: The present study further confirms that MDD is accompanied by activation of the immune system with significant elevations in the levels of four cytokines. These results indicate stimulation of the immune system and increased IR and modulation of IR by increased cytokine levels in MDD. These findings show that immune activation and associated IR are a new drug target in depression.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9635-9635
Author(s):  
T. A. Rich ◽  
M. J. Fisch ◽  
J. Manola ◽  
D. Cella ◽  
B. Ansari ◽  
...  

9635 Background: The purpose of the study was to investigate associations between fatigue, depression and pain and serum levels of proinflammatory cytokines among pts randomized to l-carnitine supplementation or placebo. Methods: 376 cancer pts with normal hemoglobin and fatigue assessed as moderate or severe were randomized to 4 wks of supplementation with oral carnitine (n=189) or placebo (n=187) 1000 mg bid. Serum levels of 10 inflammatory cytokines and growth factors were measured with Luminex bead ELISA at baseline and 4 wks for 98 pts. Wilcoxon rank sum tests were used to compare cytokine levels between arms and between pts with/without symptoms. Multivariable models of fatigue, depression and pain at 4 wks were examined, adjusting for treatment arm, baseline symptoms and baseline cytokine levels. Results: There were no statistically significant differences in cytokine levels between pts with or without severe fatigue, pain, or depression at baseline. Levels of IL-1rα were higher at baseline among pts randomized to placebo (p=0.01) and increased after 4 wks, while levels among pts randomized to l-carnitine declined (p <0.001). Levels of IFN-γ, TGF-α, IL-6, and TNF-α decreased more among pts randomized to placebo (p=0.008, p=0.006, p=0.01, and p=0.05, respectively). Pts with severe pain at 4 wks had greater declines in levels of EGF, IFN-γ, IL-1α, and IL-1rα than pts without (p=0.05, 0.05, 0.02 and 0.03, respectively). Reductions in IL-1α and TGF-α predicted lower pain severity at 4 wks (p=0.02 and p=0.04, respectively). Conclusions: Levels of proinflammatory cytokines or EGFR ligands failed to distinguish between patients with moderate vs. severe fatigue or levels of depression and pain (severe vs. not) prior to treatment intervention. Lower levels of IL-1α and TGF-α appear to be associated with improvement of pain severity but are not associated with treatment. Mechanisms for these findings require exploration. No significant financial relationships to disclose.


2018 ◽  
Vol 21 (1s) ◽  
pp. 117s-129s ◽  
Author(s):  
Navaz Karimian Pour ◽  
Micheline Piquette-Miller

PURPUSE: Bacterial co-infections and low grade endotoxemia are common in HIV patients. Inflammation due to endotoxin or HIV may influence the expression and activity of transporters. Kidney transporters influence renal drug clearances including many antiretroviral agents. Our objective was to study the effect of endotoxin and HIV on the renal expression of drug transporters in an HIV-transgenic (HIV-Tg) rat model. These rats develop immune dysfunction and AIDS-associated conditions like humans. METHODS: Endotoxin or saline was administered intraperitoneally to HIV-Tg or wild type (WT) littermates and kidneys were collected 18 hours later. Expression of transporters and cytokines were measured by qRT-PCR and Western blots. Serum cytokine levels were measured by ELISA. RESULTS: Endotoxin induced serum levels of IL-6, TNF-α and IFN-γ in both HIV-Tg and WT animals. The basal mRNA expression of Oct2, Oct3, Octn1, Mate1, Urat1 and Ent1was significantly lower (33-60%) and the expression of Ent2 and Pept2 was significantly higher (33-45%) in HIV-Tg as compared to WT. While endotoxin significantly downregulated the mRNA expression of Mdra1 and Pept2 in both HIV and WT groups (69-78%), it imposed a significant reduction on the mRNA expression of Oct2, Oct3, Octn1, Mate1, Oat2, urat1, and Ent1 (54-83%) only in the WT group. Endotoxin significantly increased the mRNA expression of Pept1 (140%) in both WT and HIV groups. CONCLUSIONS: HIV and endotoxin each imposed alterations in the expression of many clinically important renal drug transporters although co-infection did not augment this effect. Viral and/or bacterial infections may impact the renal clearance of drug substrates in patients and could potentially be a source of drug-disease interactions.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Katarzyna Tomaszewska ◽  
Magdalena Kozłowska ◽  
Andrzej Kaszuba ◽  
Aleksandra Lesiak ◽  
Joanna Narbutt ◽  
...  

Alopecia areata (AA) and vitiligo are both common skin diseases of autoimmune origin. Both alopecia areata and vitiligo have shown to be affected by oxidative stress. The present work is aimed at evaluating and comparing the serum proinflammatory cytokine levels in AA and nonsegmental vitiligo (NSV). A cross-sectional study was conducted of 33 patients with AA, 30 patients with NSV, and 30 healthy controls. Serum levels of interferon γ (IFN-γ), interleukin- (IL-) 1β, and IL-6 were determined quantitatively by ELISA method. Our analysis identified a signature of oxidative stress associated with AA and NSV, characterized by elevated levels of IFN-γ (AA: p=0.007283; NSV: p=0.038467), IL-1β (AA; NSV: p≤0.001), and IL-6 (AA; NSV: p≤0.001). IL-6 was also significantly increased in NSV patients in comparison with AA patients (p=0.004485). Our results supported the hypothesis that oxidative stress may play a significant role in promoting and amplifying the inflammatory process both in AA and vitiligo. The complex understanding of both disease etiopathogenesis involves interrelationships between oxidative stress and autoimmunity. The clinical study registration number is RNN/266/16/KE.


2019 ◽  
Vol 1 (1) ◽  
pp. 53-58
Author(s):  
Эдвард Волчек

The aim of this study was to determine the dependence of the course of liver fibrosis on the functional state of the immune system, in particular, on the imbalance of pro-inflammatory and anti-inflammatory immune reactions that are formed in patients during the development of the disease. The study included 30 patients with chronic liver diseases (18 patients with chronic hepatitis C (CHC) and 12 patients with alcoholic liver disease (ALD), 15 healthy individuals were the comparison group. Liver elastography (FibroScan) was used to evaluate liver stiffness and determine fibrosis stages according to METAVIR classification. The following cytokine levels were measured in the serum samples of the group: IL-1β, TNF-α, IL-6, IFN-γ, IL-2, IL-4, IL-8, VEGF and TGF-β. According to the data presented in this work, in patients with CHC and ALD, there was a statistically significant increase in serum levels of pro-inflammatory cytokines, namely: IL-1β, TNF-α, IFN-γ, IL-2, IL-6 and IL-8. Interestingly, elevated TGF-β values ​​were found in patients with CHC, but not in patients with ALD. Significantly lower concentrations of VEGF were observed in both study groups. There was also a significant decrease in serum IL-4 in patients with CHC, whereas in patients with ALD such a decrease was not statistically significant. Serum IL-1β content was approximately equally elevated in the early and late stages of fibrosis. A sharp rise in serum TNF-α levels occurred in the early stages of fibrosis. In the later stages, the rise in the level was replaced by a sharp fall. However, the serum levels of TNF-α in the later stages of liver fibrosis still significantly exceeded control values. The serum levels of IFN-γ in patients significantly exceeded control values without changes in different stages of fibrosis. Relatively high levels of serum IL-2 and IL-6 were noted only in the later stages of the disease. In both groups of patients, a clear dependence of serum levels of IL-8 on the stage of fibrosis was revealed. Analysis of the data allows us to conclude that immune mechanisms play a significant role in the pathogenesis of degenerative liver diseases. Therefore further studies of the mechanism and role of immune factors is required to explore possible diagnostic and therapeutic applications.


2002 ◽  
Vol 9 (4) ◽  
pp. 818-823 ◽  
Author(s):  
Rodrigo Ribeiro-Rodrigues ◽  
Tatiana Resende Co ◽  
John L. Johnson ◽  
Fabiola Ribeiro ◽  
Moises Palaci ◽  
...  

ABSTRACT Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-γ) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-γ levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-γ levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-γ immunoreactivities in serum followed kinetics in sputum. TNF-α, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-γ, however, TNF-α and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.


2022 ◽  
Vol 11 (2) ◽  
pp. 447
Author(s):  
Tomoko Takamatsu ◽  
Gaku Yamanaka ◽  
Koko Ohno ◽  
Kanako Hayashi ◽  
Yusuke Watanabe ◽  
...  

Neuroinflammation has been implicated in the pathogenesis of West syndrome (WS). Inflammatory cytokines, including interleukin-1β(IL-1β), have been reported to be associated with epilepsy. However, the assessment of cytokine changes in humans is not always simple or deterministic. This study aimed to elucidate the immunological mechanism of WS. We examined the intracellular cytokine profiles of peripheral blood cells collected from 13 patients with WS, using flow cytometry, and measured their serum cytokine levels. These were compared with those of 10 age-matched controls. We found that the WS group had significantly higher percentages of inter IL-1β, interleukin-1 receptor antagonist (IL-1RA)-positive monocytes, and interferon gamma (IFN-γ) in their CD8+ T cells than the control group. Interestingly, the group with sequelae revealed significantly lower levels of intracellular IFN-γ and IL-6 in their CD8+ T and CD4+ T cells, respectively, than the group without sequelae. There was no correlation between the ratios of positive cells and the serum levels of a particular cytokine in the WS patients. These cytokines in the peripheral immune cells might be involved in the neuroinflammation of WS, even in the absence of infectious or immune disease. Overall, an immunological approach using flow cytometry analysis might be useful for immunological studies of epilepsy.


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