Evaluation of TNF-α, IL-4, and IL-10 and parasite density in spleen and liver of L. (L.) chagasi naturally infected dogs

Dogs are the main domestic reservoirs of L. (L.) chagasi. Once in the vertebrate host, the parasite can cause visceral leishmaniasis, which can also be transmitted to humans. Cytokines are key elements of the host immune response against Leishmania spp. To investigate whether tumor necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 are associated with pattern infection in dogs, these cytokines were quantified in the spleen and liver of dogs naturally infected with L. (L.) chagasi, with or without clinical manifestations, and their levels were correlated with the parasite load verified in these organs. A total of 40 adult dogs naturally infected with L. (L.) chagasi were assessed, together with 12 uninfected control dogs. Samples from spleen and liver were used to determine the cytokine levels by capture ELISA and for quantifying parasite load by real-time PCR. Statistical analysis was performed using the minimum Chi square method and group means were compared using the Tukey test. TNF-α, IL-4 and IL-10 levels in infected dogs were higher than in control groups; the liver was the main cytokine-producing organ during infection. The level of splenic TNF-α showed correlation with parasite load and may represent an important marker for infection process evolution, with the participation of IL-10. These results may contribute to a clearer understanding of the immune response in dogs infected with L. (L.) chagasi, which may lead to the development of prophylactic or preventive measures for these animals.     

Serum Levels of Interleukins (IL)-4, IL-5, IL-13, and Interferon-γ in Acute Asthma

T-cell activation and alteration of cytokine levels are involved in the pathogenesis of bronchial asthma. However, the profile of circulating T-lymphocyte subsets and related cytokines during acute asthmatic attacks is still unclear. We hypothesized that serum levels of interleukin (IL)-4, IL-5, and IL-13 would be increased, whereas IFN-γ would be decreased in acute asthma. The subjects enrolled in this study included 58 acute asthmatics, 22 asymptomatic asthmatics, and 10 healthy controls. Serum levels of IL-4, IL-5, IL-13, and IFN-γ were measured using a sandwich enzyme-linked immunosorbent assay. We correlated serum levels of IL-4, IL-5, IL-13, and IFN-γ with initial forced expiratory volume in 1 sec (FEV₁). Compared with control subjects, acute asthmatics had significantly increased levels of circulating IL-4 (p < 0.001), IL-5 (p < 0.001), and IL-13 (p < 0.001), although the differences were of borderline significance in serum IFN-γ (p = 0.069). There were also significant differences in the circulating levels of IL-4, IL-5, and IL-13 between acute asthmatics and asymptomatic asthmatics. There was no significant association between initial FEV₁ and serum levels of IL-4 or IL-13, however, among acute asthmatics, a lower initial FEV₁ was associated with higher IL-5 and/or lower IFN-γ levels. Our results suggest that serum levels of IL-4, IL-5, and IL-13 may be elevated in acute asthma, and that higher levels of IL-5 and/or lower levels of IFN-γ are associated with severe airway obstruction.     

Analysis of polymorphisms of TNF-α, LT-α, IL-10, IL-12 and CTLA-4 in patients with warm autoimmune haemolytic anaemia

Introduction: Autoimmune haemolytic anaemia (AIHA) is defined as the increased destruction of red blood cells (RBCs) in the presence of anti‐RBC autoantibodies and/or complement. Its pathogenesis is multifactorial and includes changes in mechanisms of cytokine production and functionality. A number of recent studies have implicated cytokines polymorphisms in the pathogenesis of autoimmune diseases. The aim of this study was to determine the frequency of polymorphisms of tumour necrosis factor alpha (TNF‐α), lymphotoxin‐α (LT‐α), interleukin 10 (IL‐10), interleukin 12 (IL‐12) and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) in patients with AIHA in comparison with healthy individuals. Methods: The study population consisted of 17 patients with AIHA and 40 healthy controls. The polymorphisms for TNF‐α?308, LT‐α +252, IL‐10 ?592, IL‐12 +1188 and CTLA‐4 +49 were examined by polymerase chain reaction followed by specific restriction enzyme digestion. Results: There was no significant difference in the phenotypic distributions of polymorphisms of the TNF‐α, IL‐10, IL‐12 and CTLA‐4 between the patients and controls. Compared with healthy controls, patients with AIHA had a significant higher frequency of LT‐α (+252) AG phenotype (41%vs. 13%; P = 0.032). Conclusion: In this study, no significant differences on the frequency of TNF‐α, IL‐10, IL‐12 and CTLA‐4 polymorphisms between patients with AIHA and controls was found, suggesting that the targeted polymorphisms do not influence on the emergence and evolution of the disease. However, the LT‐α +252 polymorphism might have an effect for AIHAI development, suggesting that further studies are necessary to clear up this question.     

Clinical significance of IL-18, IL-15, IL-12 and TNF-α measurement in rheumatoid arthritis

The aim of the study was to evaluate the clinical significance of serum (S) and synovial fluid (SF) interleukin (IL)-18, IL-15, IL-12 and the tumor necrosis factor alpha (TNF-α) measurements in relation to laboratory and clinical measures of disease activity of patients with active rheumatoid arthritis (RA). Sixty-four patients with RA and 25 patients with osteoarthritis (OA) were included in this study. RA activity was determined using the Disease Activity Score (DAS) 28 index. Concentrations of IL-18, IL-15, IL-12 and TNF-α were measured by ELISA. Serum C-reactive protein (CRP) levels were also determined. Cross-sectional correlations between S and SF levels of cytokines and values of DAS 28 index were calculated. The results have shown that IL-18, IL-15, IL-12 and TNF-α levels in S and SF of patients with RA were significantly higher than the levels obtain from patients with OA (p<0.01). Significantly higher levels of IL-18, IL-15 and TNF-α were found in the SF compared to the S of patients with RA (p<0.01). Significantly higher S and SF levels of all four cytokines and serum CRP values were found in RA patients with high disease activity (DAS 28>5.1) compared to those with mild (DAS 28>3.2) and low disease activity (DAS 28>2.6) (p<0.01). Serum and SF concentrations of all four cytokines positively correlated with DAS 28 index values, i.e., disease activity. A poor correlation was found for S and SF IL-12 whereas the highest coefficient of correlation was found for SF IL-18 (r=0.879, p<0.01), and SF TNF-α (r=0.827, p<0.01) and disease activity in this study. Strong correlation was found between SF TNF-α and SF IL-18 levels (r=0.732, p<0.01). In conclusion, SF IL-18 and TNF-α levels in RA patients are good indicators of disease activity. The results obtained support the use of the DAS in clinical practice as a reliable method in assessing disease activity in RA patients.     

Biology of TNFα and IL-10, and their imbalance in heart failure

Our understanding of the multiple in vivo functions of the proinflammatory cytokine, tumor necrosis factor (TNFα), is advancing at a rapid pace. In addition to its antitumor effects, overproduction of TNFα provokes tissue injury and organ failure. TNFα has also been shown to be cardiodepressent and responsible for various cardiovascular complications. It appears that still much needs to be learned for a full comprehension of the role of TNFα in heart biology. Another cytokine, interleukin-10 (IL-10), has been shown to have anti-inflammatory properties. It is suggested to counterbalance many adverse effects of TNFα. IL-10 suppresses the production of TNFα and many other proinflammatory cytokines. TNFα-induced oxidative stress is also known to be mitigated by IL-10. Moreover, improvement in cardiac function after treatment with various drugs is also shown to be associated with an increase in IL-10 content. Based on the data reviewed in here, it is suggested that an optimal balance between IL-10 and TNFα may be a new therapeutic strategy for a healthier heart.     

Circulating IL-1β levels, polymorphisms of IL-1B, and risk of cervical cancer in Chinese women

Purpose

Long-term human papillomavirus (HPV) infection is a prerequisite for cervical cancer. IL-1β and IL-1Ra expression levels play an important role in cervical carcinogenesis. Several functional genetic variants in IL1B and IL-RN have been reported to be associated with IL-1β expression and cancer susceptibility. In the current study, we hypothesized that plasma IL-1β levels, IL-1B and IL-RN polymorphisms were candidate biomarkers for cervical cancer.

Methods

We measured plasma IL-1β levels and genotyped IL-1B and IL-RN polymorphisms in a case–control study of 404 cervical cancer cases and 404 controls in Chinese women.

Results

The mean plasma IL-1β levels in cervical cancer cases (42.19 ± 31.55 pg/ml) was significantly higher than those in controls (34.86 ± 22.68 pg/ml, P = 0.0002), and plasma IL-1β levels above the 75% quartiles in controls (IL-1β ≥ 46.94 pg/ml) were associated with a 1.74-fold significantly increased risk of cervical cancer [95% confidence interval (CI), 1.28–2.36], compared with those of lowest quartile. Multivariate logistic regression analyses revealed that the variant genotypes, IL-1B T-31C TC/CC and C-511T CT/TT, were associated with a significantly increased risk of cervical cancer [adjusted odds ratio (OR), 1.60; 95% CI, 1.16–2.21 for ?31TC/CC, and adjusted OR, 1.52; 95% CI, 1.10–2.09 for ?511CT/TT, respectively), especially among subjects having higher levels of IL-1β. However, IL-RN VNTR polymorphism was not associated with cervical cancer risk in the current study. Furthermore, the significant differences of IL-1β concentration between cervical cancer cases and controls were observed only among subjects carrying T-31C or C-511T variant genotypes.

Conclusion

Functional IL-1B genotypes may modify plasma IL-1β concentrations to contribute to the etiology of cervical cancer in Chinese women; however, further perspective studies are warranted to test the causal effects of IL-1β concentration in cervical carcinogenesis.     

Study of pro-inflammatory (TNF-α, IL-1α, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: Correlations with clinical and laboratory parameters

Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-inflammatory (TNF-, IL-1, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine levels both in plasma and SF were examined in pauciarticular and polyarticular juvenile chronic arthritis (JCA) patients during the active (n=22) and inactive (n=14) period in order to determine pathogenic mechanisms and correlations between cytokines and laboratory parameters showing disease activity. The erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and IgG concentrations were found to be significantly elevated in the active period of JCA. In pauciarticular JCA patients, when compared with their peripheral blood lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ active T cells (22.5%) were found to be significantly increased. In the active period of JCA, plasma TNF- and IL-6 concentrations were significantly elevated. Plasma IL-2 and IL-4 levels were not elevated and were found to be similar to those in the inactive phase and in healthy controls. SF IL-6, TNF- and IL-1 levels were extremely high in all the patients. SF IL-4 and IL-2 levels were all undetectable. There was a significant correlation between ESR values and plasma IL-6 levels and between serum CRP levels and plasma IL-6 and TNF- concentrations. In conclusion, increased local production of pro-inflammatory cytokines appears to account for the articular manifestations of JCA. The impaired production of anti-inflammatory Th2-derived cytokines (IL-4) seems to cause increased production of inflammatory cytokines acting on the balance between them. The deficit in IL-2 production was not suggested to be primarily involved in the pathogenesis. In addition, not only CRP and ESR values, but also plasma IL-6 and TNF- concentrations may be used as markers of disease activity.     

Correlation of High Levels of Hyaluronan and Cytokines (IL-1β, IL-6, and TGF-β) in Ascitic Fluid of Cirrhotic Patients

Our objective was to investigate the relationship between endotoxin and hyaluronan synthesis and release in serum and ascitic fluid from cirrhotic patients. We studied hyaluronan, endotoxin, albumin, and creatinine levels in ascitic fluid and plasma and cytokine levels (IL-1, IL-6, TGF-) in ascitic fluid. TGF-, IL-6, and IL-1 correlation analyses indicated a strong dependence of the production of these cytokines on endotoxin levels. Correlation analyses for TGF- and IL-6 indicated a strong dependence of the production of hyaluronan on cytokine levels and, to a lesser extent, on IL-1 levels. Hyaluronan analysis indicated that a certain glycosaminoglycan level is required in ascites before its appearance in plasma. Our results disclosed elevated plasma hyaluronan concentrations. The simultaneous increased hyaluronan levels in ascitic fluid do not seem to be derived from the systemic circulation. In conclusion, the high hyaluronan-ascites/hyaluronan-plasma ratio suggests an intrinsic hyaluronan production from peritoneal cells induced by endotoxins.     

Graves' disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

The role of genetic factors in the pathogenesis of Graves' disease (GD) is not clear. The purpose of this study was to investigate the association between single nucleotide polymorphisms in pro-inflammatory cytokine genes and GD in Iranian patients. A case-control hospital-based study was carried out on 107 GD patients and 140 healthy controls. Cytokine typing was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. The allele and genotype frequencies of the following cytokine genes were determined: TNF-α (-308A/G, -238A/G), IL-2 (-330T/G, +166G/T), IL-6 (-174C/G, A/G nt565), IL-12 (-1188A/C), and IFN-γ (UTR 5644A/T). The following alleles and genotypes were significantly overrepresented in patients: TNF-α -308A allele (P < 0.01) and AA genotype (P < 0.05), IL-2 -330G allele (P < 0.01) and GG genotype (P < 0.01), IL-6 -174C allele (P < 0.01) and CC genotype (P < 0.01), IL-12 -1188C allele (P < 0.01) and CC genotype (P < 0.01), IFN-γ UTR5644T allele (P < 0.01) and TT genotype (P < 0.01). In conclusion, this is the first study to show a significant association between GD and IL-2 -330G, IL-12 -1188C, and IFN-γ UTR 5644T alleles. Our results support the hypothesis that polymorphism in pro-inflammatory cytokines might be involved in predisposition to GD.     

Differential effect of IL-1β and TNF-α on the production of IL-6, IL-8 and PGE2 in fibroblast-like synoviocytes and THP-1 macrophages

Inflammation in the joint of rheumatoid arthritis is a complex immune reaction facilitated by various factors, such as cytokines, cells and hypoxia. Thus, we evaluated their relative capacity to produce proinflammatory mediators in response to IL-1β, TNF-α or IL-17 under hypoxia or normoxia in fibroblast-like synoviocytes (FLSs) and macrophages. The level of IL-6 expression was strongly increased in both FLSs and THP-1 macrophages in response to IL-1β and TNF-α, but the level by TNF-α was less than that by IL-1β. In contrast, the expression of IL-8 in both cell types was strongly stimulated by both IL-1β and TNF-α. In FLSs, PGE₂ production increased only in response to IL-1β; and no effect was observed in THP-1 cells and TNF-α-stimulated FLSs. In addition, the production by IL-17 was extremely low when compared with those induced by IL-1β or TNF-α in FLSs and THP-1 cells. Hypoxia (2% O₂) decreased IL-1β-stimulated production of PGE₂, even though it increased the expression of mRNA and protein of COX-2. These results suggest that IL-1β and TNF-α differentially regulate gene expression in FLSs and macrophages under hypoxia or normoxia.     

Detection of serum TNF-α,IFN-γ,IL-6 and IL-8 in patients with hepatitis B

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The Profile of the Serum Levels of Inflammatory Cytokines TNF-a, IL-6, IL-10 and Captopril Intervention in Reno-hypertensive Rats

Objectives To observe the profile of the serum levels of inflammatory cytokines interleukin-6（IL-6）, tumor necrosis factor（TNF-α）and interleukin-10 （IL-10） and evaluate the effects of angiotensin- converting enzyme inhibitor-Captopril on them in renohypertensive rats. Methods Using reformed two-kidney-one-clip （2K 1C） method, renal hypertensive rats （RHR） were obtained by ligating abdominal aorta. 30 Wistar rats were randomized into three groups： sham-operation group （A）, model control group （ B ） and captopril group （C）. All rats were killed after being given the trial drugs 5 weeks, ELISA assays were used to detect the levels of IL-6 and IL-10, the levels of TNF-alpha were measured with radioimmunoassays. Results ①compared with group A, the left ventricular hypertrophy was aggravated in group B significantly, the ratio of left ventricle and body weight（LV/BW） was 0.00318 ±0.00030 （B）and 0.00256 ±0.00040 （A） respectively（P 〈 0.001 ）, the levels of IL-6 and TNF-α increased significantly （P 〈 0.001 and P 〈 0.002 respectively）, whereas the levels of IL-10 were not changed between the two groups （P 〉 0.05）; ② compared with group B, the LV/BW was 0.00266 ± 0.00018 （C） and 0.00318±0.00030 （B） respectively（P 〈 0.001）, the levels of IL-6 and TNF-α decreased significantly （ P 〈 0.01）, whereas the levels of IL-10 were not changed between the two groups （P 〉 0.05） ; Condusions Angiotensin converting enzyme inhibitor-captopril can lower the serum levels of proinflammatory cytokines IL-6 and TNF-α effectively, but can not increase the levels of anti-inflammatory cytokine feature IL-10, it suggests that captopril may have to prevent or slow development hypertensive complications by means of levels of pro-inflammatory cytokines a of lowering the but not by increasing anti-inflammatory cytokine IL-10.     

The utility of TNF-α, IL-6 and IL-10 in the diagnosis and/or follow-up food allergy

BackgroundSeveral pro-inflammatory and anti-inflammatory mediators play a role in the immunopathogenesis of food allergy (FA). The aim of this study was to investigate the utility of serum biomarkers like interleukin (IL)-10, TNF-α, and IL-6 in the diagnosis and/or follow-up of FA.MethodsSixty (25 females, 41.6%) newly diagnosed FA patients [IgE mediated (group-1, n = 37), non-IgE (group-2, n = 23)] with a median age of nine (1–33) months were enrolled. Twenty-four healthy children with a median age of eight (1–36) months constituted the control group (CG). In all the subjects, serum TNF-α, IL-6 and IL-10 levels were evaluated at the time of diagnosis and reassessed four weeks after therapeutic elimination diet (TED).ResultsThe mean white blood cell count and median absolute eosinophile count of the CG were significantly lower than group-1 (p values were 0.019 and 0.006, respectively). The mean absolute neutrophile count and the median IL-6 were significantly higher in group-1 when compared with group-2 (p values were 0.005 and 0.032, respectively. Median TNF-α and IL-6 levels were significantly higher in the pre-TED among all patients (p values were 0.005 and 0.018, respectively). In group-1, median TNF-α and IL-6 levels decreased significantly after TED (p values were 0.01 and 0.029, respectively).ConclusionsOur findings support the role of inflammation in the pathogenesis of FA. Serum TNF-α and IL-6 levels may be useful markers for follow-up in FA, especially among IgE-mediated FA patients. Evaluation of IL-10 results was not sufficient for an interpretation of clinical tolerance.     

Bacterial Translocation Is Linked to Increased Intestinal IFN-γ, IL-4, IL-17, and mucin-2 in Cholestatic Rats

Background and rationale for the study. Bacterial translocation is an important triggering factor of infection and mortality in cirrhosis. In a rat model using bile duct ligation (BDL), bacterial translocation appears within 24 h after ligation. The dynamic between TH1/TH2/TH17 cytokines and the integrity of the colonic mucosa in the context of cirrhosis is little known. This study aims to determine the link between bacterial translocation and intestinal inflammation in a cholestasis model. Additionally, alterations of the colonic mucus layer and the bacterial load were also addressed.Results. Bacterial translocation detected by microbiological cultures and MALDI-TOF showed that Escherichia coli predominates in mesenteric lymph nodes of BDL rats. Intestinal bacterial load analyzed by qPCR indicates a dramatic Escherichia/Shigella overgrowth at 8 and 30 days post-BDL. IFN-γ, IL-4, and IL-17 evaluated by Western blotting were increased at 8 and 30 days in the small intestine. In the colon, in contrast, only IFN-γ was significantly increased. The colonic mucus layer and mucin-2 expression determined by Alcian blue staining and immunohistochemistry surprisingly showed an increase in the mucus layer thickness related to increased mucin-2 expression during the entire process of liver damage. Hepatic enzymes, as well as collagen I, collagen III, TNF-α, and IL-6 liver gene expression were increased.In conclusion, bacterial overgrowth associated with bacterial translocation is linked to the over-expression of IFN-γ, IL-4, IL-17 and mucin-2. These molecules might facilitate the intestinal permeability through exacerbating the inflammatory process and disturbing tight junctions, leading to the perpetuation of the liver damage.     

IL-10, TGF-ß, IL-2, IL-12, and IFN-γ Cytokine Gene Polymorphisms in Asthma

Asthma is a complex respiratory disease, characterized by airway inflammation and reversible airway obstruction. Both genetic and environmental factors are important in the development and expression of the disease. In order to analyze the genetic profile of Th1 and Th2 cytokines in Iranian asthmatic patients, this study was performed. The allele and genotype frequencies of a number of polymorphic genes coding for IL-10, TGF-ß, IL-2, IL-12, and IFN-γ were investigated in 60 patients with asthma in comparison with 140 controls. The most frequent genotypes in our patients were IL-10 GA at position-1082 (p = 0.001), IL-10 CT at position ?819 (p = 0.001), IL-10 CA at position ?592 (p = 0.0001), IL-12 CA at position ?1188 (p = 0.003), TGF-ß CG at codon 25 (p = 0.002), IL-2 GT at position -330 (p = 0.004). In contrast, the frequencies of the genotypes IL-10 AA at position ?1082 (p = 0.0001) and GG at position ?1082 (p = 0.01), IL-10 CC at position ?819 (p = 0.001) and TT at position -819 (p = 0.01), TGF-ß TT at codon 10 (p = 0.001), TGF-ß GG at codon 25 (p = 0.005), IL-12 AA at position ?1188 (p = 0.004), IL-2 TT at position ?330 (p = 0.01) were significantly lower in the patient group. The most frequent haplotypes in the patients were IL-10 GCC (p = 0.008) and ATA (p = 0.0001) at position ?1082, ?819, ?592, and TGF-ß CC (p = 0.036) at codon 10 and codon 25. In contrast, the frequencies of the IL-10 ACC (p = 0.001), TGF-ß TG (p = 0.024), and IL-2 TT (p = 0.001) and GT (p= 0.0001) in the patients were significantly lower than controls. Considering the high frequency of presence of IL-10 ATA haplotype and the IL-2 GT genotype, it seems that the production of IL-10 and IL-2 in the asthmatic patients could be lower than normal subjects.     

Effect of 17β-oestradiol on expression of IL-2, IL-6 and IFN-γ mRNA in human tonsillar cells

Oestradiol (E(2)) alters lymphocyte functionin vitro including T cell DNA synthesis and B cell immunoglobulin production in human tonsillar, splenic and peripheral blood cells. We have investigated whether one mechanism for this effect is that E(2) modifies the expression of IL-2, IL-6 and IFN-γ mRNA in human tonsillar mononuclear cells. Without E(2), addition of PHA (1 μg ml(-1)) for 10 h increased the expression of IL-2 and IL-6 mRNA but had no significant effect on IFN-γ mRNA. In separated T cells after 24 h incubation, E(2) (7×10(-8) M: ) increased only the IFN-γ mRNA levels. However, when E(2) was present in PHA-stimulated T cell cultures, mRNA levels from all cytokines were suppressed. E(2) decreased IL-2 mRNA levels in the T cell preparation after 24 h culture. For IL-6, E(2) decreased mRNA both in mononuclear cells and T cells after 10 h incubation. For IFN-γ, E(2) decreased mRNA levels in the mononuclear cell preparation after 24 h culture. Stimulation of the T cell preparation with PHA after 24 h incubation with E(2) decreased the IFN-γ mRNA levels compared to the cultures incubated with E(2) only. One part of the action of E(2) may be through a block in the up-regulation of the mRNA of IL-2, IL-6 and IFN-γ in activated cells.     

High Incidence of Malaria Along the Sino–Burmese Border Is Associated With Polymorphisms of CR1, IL-1A,IL-4R,IL-4, NOS,and TNF,But Not With G6PD Deficiency

Malaria is highly endemic in Yunnan Province, China, with the incidence of malaria being highest along the Sino–Burmese border.The aim of our study was to determine whether genetic polymorphisms are associated with the prevalence of malaria among Chinese residents of the Sino–Burmese border region. Fourteen otherwise healthy people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, 50 malaria patients, and 67 healthy control subjects were included in our cross-sectional study. We analyzed the frequency of the G3093T and T520C single-nucleotide polymorphisms (SNPs) of CR1. Logistic regression was used to calculate the prevalence odds ratio (POR) and 95% confidence interval (CI) of malaria for the T520C SNP of CR1 and SNPs of G6PD, IL-4, IL-4R, IL-1A, NOS, CD40LG, TNF, and LUC7L.The frequency of the 3093T/3093T genotype of CR1 in the malaria group (0.16) was significantly higher than that in the control group (0.045, P < 0.05), and significantly lower than that in the G6PD deficiency group (0.43, P < 0.01). The frequency of the 520T/520T genotype of CR1 was significantly higher in the malaria patients (0.78) than that in the control group (0.67, P < 0.05) and G6PD-deficiency group (0.36, P < 0.05). The T allele of the T520C variant of CR1 was significantly associated with the prevalence of malaria (POR: 1.460; 95% CI: 0.703–3.034). Polymorphisms of G6PD did not significantly influence the prevalence malaria (P > 0.05). A GTGTGTC haplotype consisting of IL-1A (rs17561), IL-4 (rs2243250), TNF (rs1800750), IL-4R (rs1805015), NOS (rs8078340), CD40LG (rs1126535), and LUC7L (rs1211375) was significantly associated with the prevalence of malaria (POR: 1.822, 95% CI: 0.998–3.324).The 3093G/3093G and 520T/520T genotypes are the predominant genetic variants of CR1 among Chinese residents near the Sino–Burmese border, and the T allele of T520C is associated with the prevalence of malaria in this region. Although G6PD deficiency does not protect against malaria, it may diminish the association between malaria and the CR1 polymorphisms in this population. The GTGTGTC haplotype is also associated with the prevalence of malaria in this region.     

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells,and in islets from pre-diabetic NOD mice

AIMS/HYPOTHESIS: Cytokines and chemokines are important mediators of immune responses due to their ability to recruit and activate leukocytes. Using microarray analysis we observed that rat beta cells exposed to IL-1beta and IFN-gamma have increased mRNA levels of chemokines and IL-15. The aim of this study was to characterize the expression of IP-10, MIP-3alpha, fractalkine and IL-15 in rat beta cells, human pancreatic islets, and in islets isolated from NOD mice, both during the pre-diabetic period and following islet transplantation. METHODS: FACS-purified rat beta cells and human islets were cultured with IL-1beta, IFN-gamma and/or TNF-alpha. Islets were isolated from NOD or BALB/c mice at different ages. For syngeneic islet transplantation, 2- or 3-week-old NOD islets were grafted under the kidney capsule of spontaneously diabetic NOD recipients. Chemokine and IL-15 mRNA expression and protein release were evaluated, respectively, by RT-PCR and ELISA. RESULTS: Human islets and rat beta cells express IP-10, MIP-3alpha, fractalkine and IL-15 mRNAs upon exposure to cytokines. The expression of IL-15, IP-10 and fractalkine is regulated by IFN-gamma, while the expression of MIP-3alpha is IL-1beta-dependent. Moreover, cytokines induced IL-15, IP-10, Mig, I-TAC and MIP-3alpha protein accumulation in culture medium from human islets. In vivo, there was an age-related increase in IL-15, IP-10 and MIP-3alpha expression in islets isolated from NOD mice. Following syngeneic islet transplantation, increased expression of IL-1beta, IFN-gamma, fractalkine, IP-10, MCP-1 and MIP-3alpha mRNAs were observed in the grafts. CONCLUSION/INTERPRETATION: Cytokine-exposed islets or beta cells express chemokines and IL-15. This could contribute to the recruitment and activation of mononuclear cells and development of insulitis in early Type 1 diabetes and during graft destruction.     

Elevated serum levels of TNF-α, IL-8, and ECP can be involved in the development and progression of bronchial asthma

Objective: This study aimed to explore the value of elevated serum levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and eosinophil cationic protein (ECP) in the diagnosis of bronchial asthma (BA). Methods: A total of 170 patients with BA (case group, 85 patients in acute attack and 85 patients in clinical remission) and 150 healthy individuals (control group) were enrolled in this study. Enzyme-linked immunosorbent assay and receiver operating characteristic (ROC) curves were calculated for the contents and diagnostic values of serum TNF-α, IL-8, and ECP in BA. Results: Compared with the control group, patients in acute attack and clinical remission had higher TNF-α, IL-8, and ECP levels (p < 0.05). The serum level of TNF-α was positively correlated with IL-8 and ECP (p < 0.05). ROC curves showed that the diagnostic threshold value of IL-8 was 13.53 ng/ml, its area under the curve (AUC) was 0.87, its specificity was 99.3%, and its sensitivity was 57.6%. The diagnostic threshold value of TNF-α was 1.29 ng/ml with AUC being 0.94, specificity was 89.3%, and sensitivity was 83.5%. ECP showed 7.22 ng/ml diagnostic threshold value (AUC = 0.88, specificity = 74.0%, sensitivity = 86.5%). The FEV₁/pre(%) and FEV₁/FVC were negatively correlated and the Z5/pre(%) and resonance frequency (Fres) were positively correlated with the serum levels of TNF-α, IL-8, and ECP in patients in acute attack and in clinical remission (all p < 0.05). Conclusion: Our findings reveal that elevated serum levels of TNF-α, IL-8, and ECP can be involved in the development and progression of BA.