Interleukin 17A is an immune marker for chlamydial disease severity and pathogenesis in the koala (Phascolarctos cinereus)

The koala (Phascolarctos cinereus) is an iconic Australian marsupial species that is facing many threats to its survival. Chlamydia pecorum infections are a significant contributor to this ongoing decline. A major limiting factor in our ability to manage and control chlamydial disease in koalas is a limited understanding of the koala’s cell-mediated immune response to infections by this bacterial pathogen. To identify immunological markers associated with chlamydial infection and disease in koalas, we used koala-specific Quantitative Real Time PCR (qrtPCR) assays to profile the cytokine responses of Peripheral Blood Mononuclear Cells (PBMCs) collected from 41 koalas with different stages of chlamydial disease. Target cytokines included the principal Th1 (Interferon gamma; IFNγ), Th2 (Interleukin 10; IL10), and pro-inflammatory cytokines (Tumor Necrosis Factor alpha; TNFα). A novel koala-specific IL17A qrtPCR assay was also developed as part of this study to quantitate the gene expression of this Th17 cytokine in koalas. A statistically significant higher IL17A gene expression was observed in animals with current chlamydial disease compared to animals with asymptomatic chlamydial infection. A modest up-regulation of pro-inflammatory cytokines, such as TNFα and IFNγ, was also observed in these animals with signs of current chlamydial disease. IL10 gene expression was not evident in the majority of animals from both groups. Future longitudinal studies are now required to confirm the role played by cytokines in pathology and/or protection against C. pecorum infection in the koala.     

Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency

Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency diseases. Cytokine production could be affected in CVID patients, whereas its alteration could be due to genetic polymorphisms within coding and promoter regions of the cytokine genes. This study was performed to analyse the proinflammatory cytokine single nucleotide polymorphisms in CVID. The allele and genotype frequencies of a number polymorphic genes coding tumour necrosis factor (TNF)‐α, interleukin (IL)‐1α, IL‐1β, IL‐1R, IL‐1RA and IL‐6 were investigated and compared between two groups of CVID patients and controls. The IL‐6 GA genotype at position nt565 was significantly over‐represented in the patient group (P < 0·001), while the IL‐6 GG genotype at position ?174 (P = 0·006) and the GG genotype at position nt565 (P < 0·001) were significantly lower than controls. The TNF‐α AG genotype at position ?308 in the patient group was increased significantly in comparison with controls (P = 0·027), but the GG genotype at the same position was significantly decreased (P = 0·011). IL‐6 CA and GA haplotypes were the most frequent haplotypes in the patients (P < 0·005), whereas TNF‐α GA (P = 0·002) and IL‐6 GG (P < 0·001) haplotypes were decreased significantly in the patients in comparison with controls. Cytokine single nucleotide polymorphisms could have a role in pathophysiology of CVID. High production of TNF‐α is expected in some CVID patients based on the frequency of genotypes/haplotypes of these cytokine gene polymorphisms.     

T-cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

Multifunctional interleukin 10 (IL10)⁺Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4⁺ and CD8⁺ T-cells that expressed interferon gamma (IFNγ), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFNγ, IL10 and TNF by CD4⁺ and CD8⁺ T-cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T-cells like NS3-specific IFNγ/IL10-producing CD4⁺ T-cells in critical phase and NS3- and ENV-specific CD8⁺ T-cells producing IFNγ/IL10. In addition, NS3-specific CD8⁺ T-cells producing high levels of IFNγ/TNF and IFNγ/TNF/IL10 were also observed in the mild dengue group. We observed that multifunctional T-cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T-cells. Importantly, multifunctional CD4⁺ and CD8⁺ T-cells producing IFNγ, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10⁺Th1 and IL10⁺Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.     

Dental and temporomandibular joint alterations in rheumatoid arthritis patients and their association with salivary oxidative stress

Background/aim Rheumatoid arthritis (RA) is the most extensive inflammatory arthritis causing permanent deformities in the joint. Increasing evidence suggests that oxidative stress is a substantial factor in the pathogenesis of RA. This study aimed to examine the salivary oxidant-antioxidant status of RA and control groups and to compare these biomarkers by correlating them with disease activity, acute phase reactants, and clinical findings.Materials and methods Age and sex-matched 60 participants including 30 patients with RA and 30 control (50 females, 10 males; mean age: 42.62 ± 10.89 years) were evaluated. RA disease activity and severity were evaluated by the disease activity score 28-C reactive protein (DAS 28-CRP). Rheumatoid factor (RF) positivity, anticitrullinated protein antibodies (ACPA) positivity, erythrocyte sedimentation rate (ESR), CRP, tender and swollen joint counts, and medical treatment regimens of the patients (glucocorticoids, conventional or biologic disease-modifying antirheumatic drugs) were recorded. In the radiographic examination, dental findings, and bone alterations of the temporomandibular joint (TMJ) were recorded and compared for both groups. Saliva samples were obtained for analysis of total antioxidant status (TAS), total oxidant status (TOS), arylesterase (ARE), and oxidative stress index (OSI) levels. The data analysis was conducted by independent sample t-test and chi-square test.Results Condylar erosion was the most common radiographic change in TMJ of RA patients. Osteophyte formation was a prominent finding in the control group. Lower TAS and higher OSI levels were found in RA patients compared with controls (p = 0.013; p = 0.029, respectively). The effect of DAS 28-CRP score on the levels of oxidative stress biomarkers in RA patients was not significant. Conclusion Oxidative stress causes tissue damage in response to excessive mechanical loading, which in turn promotes TMD. However, disease activity has not a prominent impact on the salivary oxidative stress status of RA patients.     

Pro-inflammatory/anti-inflammatory cytokine imbalance in acute coronary syndromes

Abstract The aim of this study was to evaluate the presence of an imbalance between proinflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We considered two groups of 26 and 28 patients with acute myocardial infarction (AMI) and unstable angina (UA) respectively, compared with a group of 30 patients with stable angina and 30 healthy volunteers. We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)γ and tumour necrosis factor (TNF)α, which are well known to possess proinflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity. We also assessed the clinical characteristics of groups and, particularly, we evaluated the circulating levels of C-reactive protein (hs-CRP). We found a significant increase of IFNγ and TNFα production (P<0.01) and a significant decrease of IL10 production (P<0.05) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes where found between AMI and UA patients and SA patients and controls. Circulating levels of hs-CRP were significantly increased (P<0.01) in patients with ACS compared with the other control groups. Our data showed an increased production of proinflammatory mediators in ACS that may be detectable both in circulating blood and in cell cultures where it is possible to evaluate in a better way the functional state of cells; this finding was associated with a reduced production of the antiinflammatory cytokine IL10. In conclusion, a relevant imbalance is present in ACS and this fact could contribute to plaque instability and clinical manifestations.     

PCT-233, a novel modulator of pro- and anti-inflammatory cytokine production

Plant extracts have been implicated in various immunoregulatory effects that are poorly understood. Thus, we investigated the modulatory activity of PureCell Complex (PCT)-233, an active molecular complex from mesophyll tissue of Spinacia oleacea on the inflammatory process. Alveolar macrophages (AM) were treated with PCT-233 and/or budesonide, a well-known anti-inflammatory agent, before or after being stimulated with lipopolysaccharides (LPS). Pro- and anti-inflammatory cytokine production, tumour necrosis factor (TNF) and interleukin (IL)-10, respectively, were measured in cell-free supernatants at different times after the treatment. PCT-233 increased unstimulated AM release of both TNF and IL-10, whereas heat- and light-inactivated PCT-233 stimulated only the release of TNF without affecting IL-10 production, suggesting that different mechanisms are involved in the modulation of TNF and IL-10 release by PCT-233. The presence of LPS did not modify PCT-233-stimulated TNF production, but the ratio TNF/IL-10 production by LPS-stimulated AM was reduced significantly in the presence of PCT-233. Pretreatment of AM with PCT-233 and budesonide before LPS stimulation reduced TNF production at both protein and mRNA levels, whereas IL-10 production was increased. Moreover, TNF/IL-10 ratio was reduced further with the combination PCT-233/budesonide. Interestingly, AM treatment with PCT-233 and budesonide 18 h after LPS stimulation did not modulate TNF release significantly but it did increase IL-10 production, and a synergistic effect was observed with the combination PCT-233/budesonide. These exciting data suggest that PCT-233 possesses some anti-inflammatory properties, even when added during the inflammatory process, and could potentiate the effect of other anti-inflammatory agents.     

IL‐6, but not IL‐4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: involvement of both mitogen‐activated protein kinases and phosphatidylinositol 3‐kinase signalling pathways

Misiak‐T?oczek A, Brzezińska‐B?aszczyk E. IL‐6, but not IL‐4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: Involvement of both mitogen‐activated protein kinases and phosphatidylinositol 3‐kinase signalling pathways. APMIS 2009; 117: 558–67. An increase in the number of mast cells within tissues is observed in many pathophysiological conditions. Current data indicate that migration of mature mast cells might be one of the key mechanisms responsible for rapid local accumulation of these cells. Considering that interleukin (IL)‐6 and IL‐4, as well as tumour necrosis factor (TNF), influence mast cell activity in various ways, the purpose of the current study was to examine whether these cytokines function as rat peritoneal mast cell chemoattractants. We showed that IL‐4, in the concentration range from 10^?6 to 10^?3 ng/ml, did not induce a mast cell migratory response, even in the presence of laminin and fibronectin. Under the same experimental conditions, mast cells were shown to migrate in response to IL‐6 stimulation in the presence of laminin. The optimal concentration of IL‐6 for maximal migration of mast cells was 10^?4 ng/ml (i.e. ～5 nM). In comparison, the optimal concentration of TNF for maximal migration of mast cells was 5 × 10^?5 ng/ml (i.e. ～3 fM). IL‐6‐stimulated mast cell migration was the result of chemokinesis, whereas TNF‐induced migration was the result of chemotaxis. Mast cell migratory responses to IL‐6 and TNF were entirely blocked by specific anti‐IL‐6R and anti‐TNFR1 antibodies. We also documented that the migration response of mast cells to stimulation with IL‐6 and TNF was mediated through signal transduction pathways involving mitogen‐activated protein kinases and phosphatidylinositol 3‐kinase. Taken together, our results indicate that IL‐6, as well as TNF, induces tissue mast cell migration. Thus, these proinflammatory cytokines can be responsible for mast cell accumulation at the site of diverse conditions accompanied by inflammation.     

Association of -1087 IL10 and -308 TNFA gene polymorphisms with serological markers of coeliac disease

Coeliac disease (CD) is known to have a strong genetic background. We analyzed the association between serological markers of CD and the –1087 IL10 and –308 TNFA gene polymorphisms in Swedish patients. A higher frequency of the TNF2 allele was present in the patients compared with the controls (p <0.0001). The frequency of the AA genotype of the IL10 gene in the patients was unexpectedly higher in comparison with the controls (p <0.05). The levels of IgA anti-endomysium and antitissue transglutaminase antibodies were associated with IL10 but not with TNFA genotype. The patients with the AA or GG –1087 IL10 genotypes had significantly lower levels of antibodies in comparison with those with the AG genotype (p <0.05 to p <0.0005). However, when divided according to potential level of IL-10 production, the group of potentially high IL-10 producers among the CD patients demonstrated significantly lower levels of antitissue transglutaminase antibodies compared to potentially low IL-10 producers (p = 0.01). Our results show a relationship between the levels of IgA antibodies involved in CD with the IL10 genotypes. This suggests a possible involvement of IL-10 in the development of the disease.     

Hibernation induces immune changes in the lung of 13-lined ground squirrels (Ictidomys tridecemlineatus)

During hibernation, significant changes occur in the systemic and intestinal immune populations. We found that the lungs of hibernating 13-lined ground squirrels (Ictidomys tridecemlineatus) also undergo shifts in immune phenotype. Within the population of mononuclear cells, the percentage of T cells increases and the percentage of CD11b/c⁺ cells decreases in hibernators. E-selectin, which promotes endothelial attachment, increases during arousal from torpor. Levels of the anti-inflammatory cytokine interleukin (IL)-10 in the lung are lower during hibernation while levels of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-α remain constant. Expression of suppressor of cytokine signaling (SOCS) proteins is also decreased in torpid hibernators. Our data point to a unique immune phenotype in the lung of hibernating ground squirrels in which certain immunosuppressive proteins are downregulated while some potentially inflammatory proteins are maintained or amplified. This indicates that the lung houses an immune population that can potentially respond to antigenic challenge during hibernation.     

Association of ESAT‐6/CFP‐10‐induced IFN‐γ, TNF‐α and IL‐10 with clinical tuberculosis: evidence from cohorts of pulmonary tuberculosis patients,household contacts and community controls in an endemic setting

Mycobacterium tuberculosis (Mtb) early secreted protein antigen 6 (ESAT‐6) and culture filtrate protein 10 (CFP‐10) are among candidate vaccines against tuberculosis (TB). Results of experimental animal models show that these antigens are associated with induction of strong T cell immunity [interferon (IFN)‐γ production], while others report that these proteins as virulent factors involved in pathogenicity of Mtb infection. However, the role of ESAT‐6/CFP‐10 during natural Mtb infections in humans has not been established. In this paper we present results of a longitudinal study from an Mtb‐infected human population from an endemic setting. Whole blood assay was used to determine levels of IFN‐γ, tumour necrosis factor (TNF)‐α and interleukin (IL)‐10 against rESAT‐6/CFP‐10 in TB patients, household contacts and community controls. The levels of IFN‐γ, TNF‐α and IL‐10 against rESAT‐6/CFP‐10 at baseline were significantly higher in patients and community controls than in household contacts. In patients, no significant difference was observed in the level of these cytokines before and after chemotherapy whereas, in contacts, the level of these cytokines increased significantly and progressively over time. The study shows that the levels of IFN‐γ, TNF‐α and IL‐10 against rESAT‐6/CFP‐10 are depressed during Mtb infection or exposure but are elevated during clinical TB. Our findings from a study of naturally infected human population suggest that IFN‐γ, TNF‐α and IL‐10 against rESAT‐6/CFP‐10 are markers for clinical TB but not for protective immunity.     

Study on the relationship between different cytokines in the semen of infertility patients

Citation
Qian L, Sun G, Zhou B, Wang G, Song J, He HM. Study on the relationship between different cytokines in the semen of infertility patients. Am J Reprod Immunol 2011; 66: 157–161 Problem The relationship between different cytokines in the semen of infertility patients was investigated. Method of study Fifty‐seven semen samples were collected from infertility and normal group at Lianyungang Maternal and Child Hospital. Routine analysis including determination of the levels of IL‐23, IL‐6, and TNF‐α was carried out. Results Density, percentage of sperm moving forward, activity, survival rate, and proportion of normal morphology of sperm of normal group were significantly higher than those of infertility group (P < 0.001). Amount and pH of the semen from the two groups showed no difference. However, there is a significant difference in IL‐23 contents of semen in the normal (5.87 pg/mL) and abnormal (11.14 pg/mL) group (P < 0.001). The correlation coefficients (R) of the contents of IL‐23 to IL‐6, IL‐8, and TNF‐α were 0.8706 (R² = 0.758, P < 0.001), 0.9725 (R² = 0.9458, P < 0.001), and 0.9499 (R² = 0.9024, P < 0.001), respectively. Conclusion IL‐23 contents of semen are different in the normal and abnormal group and have positive correlations between IL‐6, IL‐8, and TNF‐α, respectively.     

SARS病人TNFα、IFN和IL-6含量变化及其意义

目的 :动态监测SARS病人肿瘤坏死因子α(TNFα)、干扰素α(IFNα)、干扰素γ(IFNγ)和白细胞介素 6(IL 6)含量变化 ,并探讨其意义。方法 :采用酶联免疫吸附法定量检测早期、恢复期以及出院后SARS随访者 ,并选择在SARS防治一线工作但未感染的健康医护人员和普通健康体检者与之对照分析。结果 :SARS早期组TNFα均值高于其他各组 (P <0 .0 1) ;恢复期组显著高于随访组、一线对照组和健康对照组 (P <0 .0 1)。SARS早期组血清IFN α均值显著高于其他各组 (P <0 .0 0 1) ;恢复期组与一线对照组比较有统计学差异 (P<0 .0 5 )。SARS早期组血清IFN γ均值显著高于其他各组 (P <0 .0 1) ;恢复期组、随访组与一线对照组比较均有统计学意义 (P <0 .0 1)。SARS早期组IL 6显著高于其他各组 (P <0 .0 1) ;随访组与一线对照组和健康对照组间均值比较均有显著性差异 (P <0 .0 1)。结论 :SARS的发病机制中病理损伤与细胞因子IFN、TNFα和IL 6有关 ,IFN具有抗病毒作用     

The effects of water immersion and epidural analgesia on cellular immune response,neuroendocrine, and oxidative markers

Background/aim Water immersion and epidural analgesia are the most preferred pain relief methods during the labor process. Adverse effects related to these methods, impact on the labor, and perception of pain is well studied in the literature. We aimed to investigate the cord blood level of copeptin, total serum oxidant (TOS), antioxidant (TAS), interleukin (IL)-1, IL-6, and oxytocin after the labor with water immersion, epidural analgesia, and vaginal birth without pain relief. Materials and methodsThe study was conducted with 102 healthy pregnant women admitted to the obstetric delivery unit for noncomplicated term birth. Copeptin, oxytocin, TAS, TOS, IL-1, and IL-6 levels of cord blood and obstetric and neonatal results after vaginal birth were compared.Results The study included a total of 102 patients (group 1 = 30, group 2 = 30, and group 3 = 42). We found no significant difference between the three groups in terms of BMI, age, gravidity, parity, birth week, birth weight, interventional birth, perineal trauma, breastfeeding, duration of labor, oxytocin, IL-1 and IL-6 levels (p > 0.05). Neonatal intensive care unit (NICU) need, TAS, TOS, and copeptin levels were higher. Apgar scores were lower in the epidural group (p = 0.011, p = 0.036, p = 0.027, p < 0.001, and p < 0.001 respectively).Conclusion Epidural analgesia has deteriorated oxidative stress status and lower neonatal Apgar scores with higher NICU administration compared with water birth and vaginal birth without pain relief.     

Impaired cytokine responses in patients with cryopyrin‐associated periodic syndrome (CAPS)

Cryopyrin‐associated periodic syndrome (CAPS) is characterized by dysregulated inflammation with excessive interleukin (IL)‐1β activation and secretion. Neonatal‐onset multi‐system inflammatory disease (NOMID) is the most severe form. We explored cytokine responses in 32 CAPS patients before and after IL‐1β blocking therapy. We measured cytokines produced by activated peripheral blood monuclear cells (PBMCs) from treated and untreated CAPS patients after stimulation for 48 h with phytohaemagglutinin (PHA), PHA plus IL‐12, lipopolysaccharide (LPS) or LPS plus interferon (IFN)‐γ. We measured IL‐1β, IL‐6, IL‐10, tumour necrosis factor (TNF), IL‐12p70 and IFN‐γ in the supernatants. PBMCs from three untreated CAPS patients were cultured in the presence of the IL‐1β blocker Anakinra. Fifty healthy individuals served as controls. CAPS patients had high spontaneous production of IL‐1β, IL‐6, TNF and IFN‐γ by unstimulated cells. However, stimulation indexes (SIs, ratio of stimulated to unstimulated production) of these cytokines to PHA and LPS were low in NOMID patients compared to controls. Unstimulated IL‐10 and IL‐12p70 production was normal, but up‐regulation after PHA and LPS was also low. LPS plus IFN‐γ inadequately up‐regulated the production of IL‐1β, IL‐6, TNF and IL‐10 in CAPS patients. In‐vitro but not in‐vivo treatment with Anakinra improved SIs by lowering spontaneous cytokine production. However, in‐vitro treatment did not improve the low stimulated cytokine levels. Activating mutations in NLRP3 in CAPS are correlated with poor SIs to PHA, LPS and IFN‐γ. The impairment in stimulated cytokine responses in spite of IL‐1β blocking therapy suggests a broader intrinsic defect in CAPS patients, which is not corrected by targeting IL‐1β.     

血浆IL-6、TNF-α和皮质醇（8：00和24：00）水平诊断脑损伤严重程度的临床应用

目的：血浆IL-6、TNF-α和皮质醇（8：00和24：00）水平诊断脑损伤严重程度的临床应用。方法：检测112例脑损伤患者和59例正常对照组血浆IL-6、TNF-α和皮质醇（8：00和24：00）水平并做了比较分析。结果：112例脑损伤被分成重度、中度和轻度三组。112例脑损伤中IL-6、TNF-α和皮质醇（8：00和24：00）水平明显高于58例正常对照组,并随着脑损伤的严重程度,血浆IL-6、TNF-α和皮质醇（8：00和24：00）水平不断增加,与正常对照组比较（P均〈0.01）。重度脑损伤血浆IL-6、TNF-α和皮质醇（8：00和24：00）水平明显高于中度和轻度脑损伤（P〈0.05）。中度者稍高于轻度者但无明显差异（P〉0.05）。结论：血浆IL-6、TNF-α和皮质醇（8：00和24：00）测定是临床上诊断脑损伤严重程度的良好指标,并可据此采取必要的治疗手段。     

IgG1 antimycobacterial antibodies can reverse the inhibitory effect of pentoxifylline on tumour necrosis factor alpha (TNF-alpha) secreted by mycobacterial antigen-stimulated adherent cells

Chronic inflammation associated with cachexia, weight loss, fever and arthralgia is the hallmark of advanced mycobacterial diseases. These symptoms are attributed to the chronic stimulation of tumour necrosis factor (TNF)-alpha. Mycobacterial components directly stimulate adherent cells to secrete TNF-alpha. We have shown recently that IgG1 antimycobacterial antibodies play a role in augmenting TNF-alpha in purified protein derivative (PPD)-stimulated adherent cells from non-BCG-vaccinated donors. We now show that IgG1 antibodies can also augment TNF-alpha expression in stimulated adherent cells obtained from BCG-vaccinated donors and this augmentation is not linked to interleukin (IL)-10 secretion. In addition IgG1 antimycobacterial antibodies can reverse the effect of TNF-alpha blockers such as pentoxifylline and thalidomide. These studies therefore have clinical implications for anti-inflammatory drug treatments which are used increasingly to alleviate symptoms associated with chronic inflammation.     

Tumor Necrosis Factor and Interleukin‐6 Gene Polymorphisms and Endometriosis Risk in Asians: A Systematic Review and Meta‐Analysis

A relationship between endometriosis and tumor necrosis factor (TNF‐α) and interleukin‐6 (IL‐6) gene polymorphisms has been raised for Asians. However, this topic is controversial. This study was a meta‐analysis to explore whether TNF‐α/IL‐6 gene polymorphisms were associated with a risk of endometriosis in Asians. By searching PubMed, HuGENet, and China National Knowledge Infrastructure (CNKI) databases, 17 studies were identified and included (3372 cases and 4008 controls). The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between TNF‐α/IL‐6 gene polymorphisms and endometriosis risk. An association of TNF‐α gene ‐1031T/C polymorphism with endometriosis was found (TT + TC vs. CC: OR 0.50, 95% CI 0.30–0.82, I² = 37.1%, P = 0.20; TT vs. CC: OR 0.50, 95% CI 0.30–0.82, I² = 43.0%, P = 0.173; TC vs. CC: OR 0.49, 95% CI 0.29–0.83, I² = 10.6%, P = 0.327). In addition, TNF‐α‐238A/G and IL‐6 ‐174C/G gene polymorphisms were also likely to be associated with endometriosis in Asians. For the TNF‐α‐238A/G gene polymorphism, the OR was 1.577 (95% CI: 1.01–2.48). For the IL‐6 ‐174C/G gene polymorphism, the OR was 1.554 (95% CI: 1.04–2.31). No associations were detected between the TNF‐α‐308A/G and IL‐6 ‐634C/G polymorphisms and susceptibility to endometriosis. Our results indicate that the TNF‐α gene ‐1031T/C polymorphism can reduce the risk of endometriosis, but for Asians, TNF‐α‐238A/G and IL‐6 ‐174C/G gene polymorphisms may be a risk factor for endometriosis. No association was found for the TNF‐α‐308A/G and IL‐6 ‐634C/G gene polymorphisms.     

Anti‐tumour necrosis factor treatment increases circulating T helper type 17 cells similarly in different types of inflammatory arthritis

We investigated changes in circulating T helper type 17 (Th17) cells following anti‐tumour necrosis factor (TNF) in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMC) were isolated from 25 RA, 15 AS and eight PsA patients at baseline 4 and 12 weeks after treatment, and Th17 cell frequencies were analysed using interleukin (IL)‐17 enzyme‐linked immunospot (ELISPOT) and flow cytometry. A significant increase in IL‐17‐producing cells was observed by ELISPOT in RA and AS patients at 12 weeks. Flow cytometry confirmed significant increases in CD4⁺IL‐17⁺ cells at 12 weeks in RA and AS and 4 weeks in PsA patients. Anti‐TNF treatment increases circulating Th17 cells in three different diseases.     

Assessment of Inflammatory Biomarkers and Oxidative Stress in Pulmonary Thromboembolism: Follow-up Results

Instability in circulation, hypoperfusion, hypoxia, and ischemia in pulmonary thromboembolism (PTE) may occur as a result of failure in pulmonary circulation. All these conditions cause inflammation and oxidative stress. We aimed to investigate inflammatory markers, asymmetric dimethylarginine (ADMA) levels, and the oxidant-antioxidant balance in patients with PTE. This study was conducted as a prospective case-control study. Thirty-eight patients with PTE enrolled to the study. Age- and gender-matched 38 healthy subjects without risk factors for pulmonary embolism were selected as control group. Venous blood samples were obtained from the PTE patients during the initial diagnosis and at the first month of treatment and from the control subjects. Interleukine-6 (IL-6), tumor necrosis factor alpha (TNF-α), total antioxidant status (TAS), total oxidant status (TOS), and ADMA levels were measured for all the samples. The results of patients and healthy subjects were compared. The mean age of the control group was 51.81?±?15.18 years, and the mean age of the patients was 52.90?±?18.22 years (p?=?0.770). Deep venous thrombosis was present in 68 % of the patients. While we found significant differences between the patient and control groups in terms of IL-6, TAS, TNF-α, ADMA and oxidative stress index (OSI) values (p?=?0.001, p?=?0.011, p?=?0.038, p?=?0.028, and p?=?0.024, respectively), the TOS value was not different between the groups (p?=?0.080). The ADMA, TNF-α, TAS, TOS, and OSI values of the patients during the initial diagnosis and at the first month of treatment were not different (p?>?0.05). The results of this study indicate an increased inflammation, endothelial damage, and oxidative stress in PTE. No difference at the first month of therapy suggests ongoing processes. We consider that these markers may be useful in the diagnosis and follow up of PTE.     

In vitro immunomodulatory activity of celastrol against influenza A virus infection

Context: The influenza A virus (IAV) causes severe respiratory disease that remains a leading reason for morbidity and mortality. Previous studies have indicated that influenza complications in addition to viral replication are due to overproduction of pro-inflammatory cytokines. Therefore, a new compound is needed to be used with current antiviral drugs to modulate overproduction of pro-inflammatory cytokines in IAV infection.

Objective: This study investigated the effect of celastrol on mRNA expression and concentration levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) that are induced by influenza A/Puerto Rico/8/34 (H1N1; PR8) in Madin-Darby Canine Kidney (MDCK) cells. The effect of this compound on virus titration and viral mRNA expression was also investigated.

Methods: Confluent MDCK cells were infected with influenza virus (H1N1; PR8) and treated with celastrol at different concentrations. After incubation, mRNA expression and concentrations of TNFα and IL6 were investigated using real-time polymerase chain reaction (PCR) and ELISA. The viral mRNA expression and virus titration were investigated using real-time PCR and 50% tissue culture infectious dose (TCID₅₀) assay, respectively.

Results: mRNA expression and concentrations of TNFα and IL6 increased significantly in control virus compared to cell control, and decreased significantly when compared with control virus after celastrol treatment. Viral mRNA expression and virus titration did not decrease after celastrol treatment.

Conclusion: Due to reducing mRNA expression and concentrations of TNFα and IL6, celastrol can serve as a suitable choice to control cytokine-induced inflammation in IAV infection, and therefore it can be used with current antiviral drugs.