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.     

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.     

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.     

Associations between polymorphisms in IL-12A, IL-12B, IL-12Rβ1, IL-27 gene and serum levels of IL-12p40, IL-27p28 with esophageal cancer

Purpose

The aim of this study was to investigate whether IL-12A, IL-12B, IL-12Rβ1, and IL-27 gene polymorphisms and serum levels of IL-12, IL-27 are associated with esophageal cancer.

Methods

We genotyped IL-12A gene rs568408, IL-12B gene rs3212227, IL-12Rβ1 gene 378 C/G, IL-27 gene rs153109, rs17855750, and rs181206 polymorphisms in a case–control study of 426 esophageal cancer patients and 432 health controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay.

Results

Both serum IL-12p40 and IL-27p28 levels were significantly higher in controls than those in patients (P?<?0.01). Rs568408 AG/AA, rs3212227 CC/AC, and IL-12Rβ1 378 GG/GC genotypes were associated with significantly increased risk of esophageal cancer (rs568408: χ²?=?5.704, P?=?0.017; rs3212227: χ²?=?7.689, P?=?0.006; IL-12Rβ1 378C/G: χ²?=?5.206, P?=?0.023). Moreover, rs3212227 CC/AC and 378 GG/GC genotypes were observed significantly associated with decreased serum IL-12p40 level in patients compare to other genotypes (rs3212227: t?=?2.129, P?=?0.034; IL-12Rβ1 378 C/G: t?=?2.178, P?=?0.030). Furthermore, frequency of rs3212227 CC/AC genotypes was significantly higher in patients with poor differentiation than those with AA genotype (χ²?=?4.314, P?=?0.035).

Conclusion

Our data suggest that the impaired production of IL-12p40 and IL-27p28 behaves as risk factors for esophageal cancer occurrence. IL-12B gene rs3212227 CC/AC and IL-12Rβ1 gene 378 GG/GC genotypes, which associated with decreased IL-12p40 level, may contribute to esophageal cancer susceptibility.     

Modulation of IL-1β, IL-6, IL-8, TNF-α, and TGF-β secretions by alveolar macrophages under NO2 exposure

Activated alveolar macrophages (AMs) secrete interleukine (IL)1, IL-6, IL-8, tumor necrosis factor- (TNF-), and transforming growth factor- (TGF-), whose inflammatory and fibroblast-activating characteristics may play a role in the maintenance of pulmonary inflammatory processes and subsequent fibrosis. Human AMs were transferred to a gas cylinder and exposed to NO₂ in concentrations ranging from 0.1 to 0.5 ppm in synthetic air for 30 min at 37°C. AMs were fixed on a polycarbonate membrane and placed on culture medium. A culture was established, with the exposed AM (nonstimulated or stimulated with 1 g/ml lipopolysaccharide [LPS]), and the remaining cells were used to determine the cytokines. IL-1, IL-6, and IL-8 were quantified by commercial enzyme-linked immunosorbent assay kits (ELISA kits). TNF- was determined with a sandwich ELISA, using the biotin-streptavidin system. NO₂ exposure of nonstimulated AM did not result in changes in IL-1, IL-6, TNF-, and TGF- release, compared to the situation with control experiments. Exposure for 30 min to NO₂ induced a significant decrease of LPS-stimulated IL-1, IL-6, IL-8, and TNF- (p < .05). The release of TGF- was not significantly affected by NO₂ exposure. Cytotoxicity of AM was checked by trypan blue exclusion, with values ranging from 1.3 to 3.0%. NO₂ exposure of LPS-stimulated AM resulted in a functional impairment of AM after NO₂ exposure regarding IL-1, IL-6, IL-8, and TNF-. Neither the spontaneous nor the stimulated release of TGF- were influenced by NO₂.     

Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity

Natural killer-22 (NK-22) cells are a human NK cell subset situated in mucosal-associated lymphoid tissues that specialize in IL-22 secretion in response to IL-23. Here we investigated the cytokine requirements for NK-22 cell expansion. IL-7 maintained the sur-vival of NK-22 cells and IL-22 production in response to IL-23 but was insufficient to induce robust expansion. Proliferation of NK-22 cells was increased markedly by adding either IL-1β or IL-2 to IL-7 and was even stronger in the presence of IL-1β plus IL-2. In contrast to IL-7, continuous culture in IL-1β and IL-2 modified NK-22 cytokine profiles. IL-1β promoted constitutive IL-22 secretion rather than acute IL-22 production in response to IL-23 and induced IL-17 in some cells. IL-2 reduced secretion of IL-22 and IL-17, increasing production of IFN-γ and leukemia inhibitory factor. Functional deviation toward IFN-γ production also was induced by continuous culture in IL-23. These results demonstrate the functional plasticity of NK-22 cells, which may allow flexible responses to different pathogens. Finally, we found that NK-22 cells released the B-cell survival factor, B-cell activating factor belonging to the TNF family (BAFF), suggesting a potential role of NK-22 cells in promoting B-cell–mediated mucosal immunity.     

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.     

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.     

Preliminary analysis of single-nucleotide polymorphisms in IL-10, IL-4, and IL-4Rα genes and profile of circulating cytokines in patients with gastric Cancer

Background

Gastric Cancer is highly prevalent and deadly worldwide. In Colombia, it is the most lethal form of cancer. Some single-nucleotide polymorphisms in IL-10, IL-4, and IL-4Rα genes have been associated with an anti-inflammatory environment and a Th2 profile in detriment of the antitumor Th1 response. This research sought to detect single-nucleotide polymorphisms in promoter sequences, like ??1082 (G/A), ??592 (C/A), and???819 (C/T), as well as ??590 (C/T) of the IL-10 and IL-4 genes, respectively; in addition to the IL-4Rα mutation variants, Ile50Val and Q576R, together with circulating levels of IL-4, TNF-α, IL-10, and IFN-γ in patients with gastric carcinoma in Cúcuta, Colombia.

Methods

In a cross-sectional study, 17 patients and 30 healthy individuals were genotyped for the six polymorphisms mentioned through PCR-RFLP of DNA obtained from peripheral blood cells and serum samples were analyzed by sandwich ELISA to quantify cytokines. Statistical difference between groups was determined along with the association between the presence of polymorphisms and the risk of gastric cancer, as well as the mortality in patients, using Mann-Whitney U test and logistic regression analysis, respectively.

Results

An association between the ??1082 (G/A) and the risk of gastric cancer was found (OR?=?7.58, range 0.77–74.06, P?=?0.08). Furthermore, patients had a significant increase in IL-4 serum levels (P?<?0.01) compared to healthy individuals, both variables showed a higher estimated risk of mortality in patients, although without statistical association (P?>?0.05).

Conclusion

We infer that two possible biomarkers (one immunological and one genetic) could be considered in association with gastric cancer in our population, which should be confirmed by subsequent studies involving a greater number of individuals.

     

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.     

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.     

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

ＮＴＲＯＤＵＣＴＩＯＮＳｉｎｃｅＭｕｔｏ［１］ｒｅｐｏｒｔｅｄｔｈａｔＴＮＦαａｎｄＩＬ１ｗｅｒｅｒｅｌａｔｅｄｔｏｆｕｌｍｉｎａｎｔｈｅｐａｔｉｔｉｓ,ｔｈｅｓｔｕｄｉｅｓｏｎｔｈｅｒｅｌａｔｉｏｎｓｈｉｐｂｅｔｗｅｅｎｃｙｔｏｋｉｎｅｓａ...     

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.     

Dialysate leukocytes, sICAM-1, hyaluronan and IL-6: predictors of outcome of peritonitis?

BACKGROUND/AIMS: Despite effective antibiotic therapy, peritonitis still remains a major problem in peritoneal dialysis (PD). The aim of the present study was to investigate changes of CRP, dialysate leukocytes and IL-6, hyaluronan (HA) and sICAM-1 in dialysate during and after peritonitis and their association to the outcome of peritonitis. METHODS: Dialysate IL-6, HA and sICAM-1 were measured at the onset and on day 4, at the end of the treatment and 2 months after onset of peritonitis. Furthermore, CRP and dialysate leukocytes were measured on days 1-4. RESULTS: All measured soluble factors were higher on the first and fourth day than at the end of the treatment. sICAM-1 and HA were lower at the end of the treatment in patients who later had a relapse/re-infection. IL-6 remained higher 2 months after clinically cured peritonitis. CRP and dialysate leukocytes were higher on day 4 in patients with poor outcome. CONCLUSIONS: Peritonitis causes increased excretion of soluble factors. Low concentrations of sICAM-1 and HA at the end of the treatment were negative prognostic indicators. Higher IL-6 levels after peritonitis could be a sign of ongoing inflammation in the peritoneal membrane. Delayed decrease in CRP and dialysate leukocytes may indicate poor outcome.     

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.     

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.     

IL-1β, IL-6, IL-8, IL-10, IFN-γ, TNF-α and its relationship with lipid parameters in patients with major depression

There is some evidence that an immune response with an increased production of proinflammatory cytokines frequently accompanies major depression. The aim of this study was to determine the serum levels of interleukines (IL-1??, IL-6, IL-8, IL-10), tumor necrosis factor-alpha (TNF-??), interferon-gamma (IFN-??) and immonuglobulines (IgG, IgA and IgM) levels and to examine the relationships between all above parameters and lipid parameters. The study group included 30 patients and 30 healthy volunteers. Although total cholesterol, HDL-cholesterol, and IgM levels were increased significantly (p?<?0.05) in patients and compared to those of the controls, no statistically significant differences (p?>?0.05) were observed with other parameters. IFN-?? were positively correlated with total cholesterol (r?=?0.425; P?=?0.019) and LDL-cholesterol (r?=?0.391; P?=?0.032) levels in patients. Other cytokines and immunoglobulins did not show any correlation with lipid parameters. It was concluded that although no differences was observed in cytokines and immunoglobulin levels in the present study, the dysregulation of the lipids and immune system including the cytokine network is associated with the etiology and pathophysiology of major depressive disorders.     

Clinical efficacy of Anchang formula for treating acute radiation enteritis and its effects on serum expressions of IL-2,IFN-γ,and IL-10

正Objective To observe clinical efficacy of Anchang Formula (AF) for treating acute radiation enteritis and its effects on serum expressions of IL-2, IFN-γ, and IL-10.Methods Totally 93 patients with acute radiation enteritis were assigned to two groups by random digit table,the treatment group (48 cases) and the control group(45 cases). Patients in the treatment group received retention enema of AF, while those in the control group received retention enema of normal saline, dexamethasone,and montmorillonite powder. The treatment course was14 days. The total clinical efficacy, enteroscope effica-     

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.     

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.