Significant Decrease In IL-4 Research Articles

The TBX21 transcription factor T-1993C polymorphism is associated with decreased IFN-γ and IL-4 production by primary human lymphocytes

T-bet is a transcription factor that drives the Th1 immune response primarily through promoting expression of the IFN-γ gene. Polymorphisms in the T-bet gene, TBX21, have been associated with immune-mediated diseases such as asthma and systemic sclerosis. We found that the TBX21 promoter polymorphism T-1993C is associated with a significant decrease in IL-4 and IFN-γ production by stimulated primary human lymphocytes from healthy participants.

English

This study aimed to investigate the effect and mechanism of tranilast (TR) on bleomycin (BLM) induced pulmonary fibrosis in a rat model, pulmonary fibrosis was induced in rats by using intratracheal bleomycin and the serum and lungs were collected 28 days later. The serum levels of IL-4 and IFN-γ were determined by ELISA and IL-4/IFN-γ was calculated. Reverse transcription polymerase chain reaction (RT-PCR) was employed to measure the mRNA expression of TGF-β1. Immunohistochemistry was employed to detect the protein expression of TGF-β1 followed by evaluation of alveolitis and fibrosis. When compared with BLM group and glucocorticoid (GC) group, the INF-γ level was markedly increased and IL-4 level dramatically decreased in the TR group with a significant decrease of IL-4/INF-γ ratio. The mean optical density and mRNA expression of TGF-β1 were markedly decreased accompanied by low scores of alveolitis and fibrosis. Significant differences were observed between TR groups (medium and high dose) and BLM group as well as control group (P < 0.05) in the aforementioned parameters. Moreover, marked difference was also observed among TR groups (P < 0.05) in the aforementioned parameters. Both TR and GC can affect the Th1/Th2 lymphocyte balance and inhibit the TGF-β1 expression improving the BLM induced pulmonary fibrosis. Key words: Th1/Th2, tranilast, pulmonary fibrosis, interferon-γ, transforming growth factor-β1.

Impact of the hypomethylating agent 5-azacytidine on dendritic cells function

Recent evidence suggested that 5-azacytidine (5-aza) can impact important immune functions via epigenetic modifications, making it an attractive candidate for pharmacologic manipulation of the immune system. The aim of this work was to study the effects of 5-aza on human dendritic cells (DC) generated from peripheral blood monocytes, and to test the type of immune response induced in patients treated with 5-aza. On the phenotypic level, CD40 and CD86 expression was significantly increased on mature DC exposed to 5-aza (5-aza-DC), compared with control untreated DC. Mature control DC and mature 5-aza-DC secreted comparable amounts of interleukin (IL)-6, IL-12p70, IL-23, and tumor necrosis factor-α. However, mature 5-aza-DC secreted significantly lower levels of IL-10 and IL-27 compared to mature control DC (p = 0.04 and p = 0.005, respectively). In the peripheral blood of 14 patients (7 males and 7 females; age range, 53-81 years) with advanced myeloid malignancies (8 acute myeloid leukemia and 6 myelodysplastic syndrome) treated with 5-aza, there was a significant decrease of IL-4-secreting CD4(+) T cells (p = 0.001), and a significant increase of IL-17A- and IL-21-secreting CD4(+) T cells (p = 0.003 and p = 0.01, respectively, compared to 5 healthy donors) suggesting a Th17 response pattern in the blood of patients receiving 5-aza. In all, these data suggest potentially novel mechanisms of action of epigenetic therapies, such as 5-aza, which may have broader implications for immunotherapeutic strategies.

Third-Generation Fatty Emulsions as Part of Parenteral Feeding in Operated Cancer Patients

Objective: to study the efficacy of third- versus secondary-generation fatty emulsions as part of parenteral nutrition in patients operated on for gastric cancer. Subjects and methods. Envelope randomization was used to make up two groups, each comprising 10 patients, operated on for gastric cancer in the scope of gastrectomy. A control group received parenteral nutrition having the following components: Lipofundin MST/LST 20%, (500 ml daily) + Nutriflex 48/150 (B. Braun) (1000 ml daily, 1744 kcal/day). The study group patients were given Lipoplus 20% (500 ml daily) + Nutriflex 48/150 (1000 ml daily, 1745 kcal/day). Parenteral nutrition was used on postoperative days 1 to 5. Results. Nutritional status evaluation revealed a significant increase in the concentration of total protein and albumin in the control and study group patients on postoperative day 6. The use of both second- and third-generation fatty emulsions caused a significant increase in the concentration of triglycerides on day 6 after surgery; no differences were found between the groups. On day 6 following surgery, there was a significant decrease in IL-4 in both groups (p&lt;0.05). At the same time the Lipofundin MST/LST group showed a significantly lower concentration of IL-4 than did the study group (p&lt;0.05). After termination of a parenteral nutrition course, the study and control groups showed a significant decrease in one of the major pro-inflammatory cytokines — IL-6. Conclusion. In the study group, the serum anti-inflammatory activity of IL-4 was more evident than that in the control group and the proinflammatory activity (IL-6 concentration) decreased, which can support that as compared with the second-generation fatty emulsions, third-generation ones with a balanced omega 3 to omega-6 fatty acid ratio (1:2.7) had a normalizing effect on systemic inflammatory processes and cytokine balance with increased anti-inflammatory and reduced proinflammatory activities. Key words: third-generation fatty emulsions, omega-3/omega-6 fatty acids, pro and anti-inflammatory cytokines.

Helminth infection inhibits airway allergic reaction and dendritic cells are involved in the modulation process

Several previous studies have demonstrated that some helminth infections can inhibit allergic reactions, but the examination on the effect of live Schistosoma japonicum (SJ) infection on allergic inflammation remains limited. The aim of this study was to examine the effect and mechanism of chronic SJ infection on airway allergic inflammation in a murine model. The data showed that chronic SJ infection suppressed airway eosinophilia, mucus production and antigen-specific IgE responses induced by ovalbumin (OVA) sensitization and challenge. Cytokine production analysis showed that chronic SJ infection reduced allergen-driven interleukin (IL)-4 and IL-5 production, but had no significant effect on IFN-gamma production. More importantly, we found that the adoptive transfer of dendritic cells (DCs) from SJ-infected mice dramatically decreased airway allergic inflammation in the recipients, which was associated with significant decrease of IL-4/IL-5 production and increase of IL-10 production. The results suggest that SJ infection may inhibit the development of allergy and that DCs may be involved in the process of helminth infection-mediated modulation of allergic inflammation.

TACI‐Ig prevents the development of airway hyperresponsiveness in a murine model of asthma

Increased levels of serum IgE are associated with greater asthma prevalence and disease severity. IgE depletion using an anti-IgE monoclonal antibody has met with success in the treatment of moderate-to-severe and severe persistent allergic asthma. To test whether B cell-targeted therapy is a more effective treatment for airway hyperresponsiveness (AHR) in a murine model compared with IgE-depletion. We delivered soluble mTACI-Ig, a receptor for the B cell survival factors BLyS (B Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), or anti-IgE to allergen-sensitized mice before airway challenge with allergen. mTACI-Ig treatment reduced circulating mature B cell levels in the blood, while anti-IgE treatment had no effect on B cell counts. Both mTACI-Ig and anti-IgE decreased the levels of total and allergen-specific IgE in the serum. Histopathologic analysis of lungs showed a reduction in disease severity scores for both treatment groups, but results were more pronounced in mTACI-Ig-treated mice. Neutrophil and eosinophil numbers in the bronchoalveolar lavage (BAL) were significantly reduced following mTACI-Ig treatment, but not after anti-IgE delivery. BLyS and APRIL blockade also resulted in a significant decrease in IL-4 and eotaxin mRNA and IL-4 and KC protein levels in total lung homogenates and BAL fluid, respectively. Finally, mTACI-Ig treatment was more effective than anti-IgE treatment in reducing AHR to inhaled antigen. Our data demonstrate that delivery of mTACI-Ig is a more effective treatment than anti-IgE mAb in a murine model of AHR.

Discrepancies of NKT cells expression in peripheral blood and in cerebrospinal fluid from Behçet's disease

The precise role of natural killer T (NKT) cells in the pathogenesis of Behçet's disease (BD) remains unknown. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMC) from 42 BD patients and in cerebrospinal fluid (CSF) samples from 9 neuro-BD patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMC from BD patients (median: 0.06%; range: 0%–0.3%) when compared to healthy controls (median: 0.23%; range: 0.1%–0.7%; P < 0.01). NKT cells were biased toward a Th 1-like phenotype, with a significant decrease of IL-4/IFN-γ ratio in BD (median: 0.049; range: 0.01–0.13) vs. healthy controls (median: 0.82; range: 0.4–1.33; P < 0.01). NKT cells were increased in CSF–BD samples (median: 0.18%; range: 0.1%–0.4%), when compared to CSF–NIND patients (median: 0.05%; range: 0.01%–0.09%; P < 0.01). Based on the reactivity of PBMC-derived NKT cells toward α-galactosylceramide (α-GalCer), 80% of BD patients were non-responsive. At the opposite, the reactivity of NKT cells in CSF from BD patients was not impaired. BD–CSF NKT cells exhibited an increased expression of IFN-γ-producing cells, demonstrating that CSF-NKT cells were functional, and biased toward a Th 1-like phenotype. These data suggest that functional NKT cells are recruited into BD inflammatory sites contributing to BD pathogenesis.

Th1 shift in CIDP versus Th2 shift in vasculitic neuropathy in CSF

To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-γ, TNF-α, G-CSF, MCP-1 and MIP-1β, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-γ and IL-4 in CSF CD4 + T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4 + T cells, IFN-γ + IL-4 − cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-γ/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-γ − IL-4 + CD4 + T cell percentage, and tended to have a higher intracellular IFN-γ/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-γ-producing CD4 + T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.

Pre-exposure effects of 1 and 3 MHz therapeutic ultrasound on ConA activated spleenocytes.

This study was performed to evaluate the pre-exposure effects of ultrasound (1 MHz or 3 MHz) on ConA activated spleenocyte proliferation and cytokine production. Cells were treated for 10 min at various intensities, rested for 1h and stimulated with the T cell activator ConA. The cells were then analyzed for the effects of non-thermal ultrasound on cell growth and the presence of IL-2, IL-4 and IFN-g. The data show that pre-exposure of spleenocytes had no significant effects on the proliferation of ConA activated spleenocytes at either 1 or 3 MHz (10 min at 0.1 or 0.5 W/cm(2)). Significant increases in IL-2 were observed in both 1 and 3 MHz pre-treated and ConA activated spleenocytes. Cells pre-treated with 1 MHz and stimulated with ConA showed a significant increase in IL-4 and IFN-g. Conversely, cells pre-treated with 3 MHz and stimulated with ConA show a significant decrease in IL-4 and IFN-g. Interleuken-4 is known to increase the growth of mast cells, inhibit macrophage activation and increases the activity of the T cell subpopulation, T(H2). Interferon-gamma is known to stimulate production of collagen in fibroblasts, enhance debridement activity of macrophage and inhibit activity of the T cell subpopulation, T(H2).

Are cytokines linked to collagen breakdown during periodontal disease progression?

Evidence of the role of cytokines produced by resident and inflammatory cells during inflammation is well established. The aim of this study was to quantify in healthy and diseased human gingiva the area fraction (AA%) occupied by collagen fibers and the amount of cytokines such as interleukin (IL)-1beta, IL-4, IL-6, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and epidermal growth factor (EGF) to investigate a possible correlation between such cytokines, collagen degradation, and the gingival index. Gingival tissue specimens from 6 healthy controls (group 1), 6 patients with mild gingival inflammation (group 2), 6 patients with moderate gingival inflammation (group 3), and 6 patients with severe gingival inflammation (group 4) were cultured for 72 hours, and the cytokines present in the culture media were quantified using an enzyme-linked immunosorbent assay (ELISA). Paraffin gingival sections from the 24 subjects were stained with sirius red F3Ba for visualization of collagen fibers, then the area fraction (AA%) occupied by the gingival fibers was determined by automated image analysis. The present study revealed significant differences (P < 0.05) between means of AA% in group 1 (53%), group 2 (41%), group 3 (39.5%), and group 4 (35%) for collagen fibers. Compared to controls, there were significant increases of IL-1beta (groups 3 and 4), IL-6, and TNF-alpha (group 3); a significant decrease of IL-4 (groups 2, 3, and 4) and TGF-beta (groups-2 and, 3); and no change of EGF. The collagen AA% was significantly correlated with the amounts of IL-4 and TGF-beta, and significantly inversely correlated with the amounts of IL-1beta for all 3 inflamed groups and IL-6 and TNF-alpha for groups 2 and 3. The present study showed that EGF was not changed in inflamed gingival tissue and that IL-1beta and IL-4 were particularly and intensively correlated with collagen loss. These 2 cytokines could be markers of clinical severity during active periodontitis.

Mosquito feeding modulates Th1 and Th2 cytokines in flavivirus susceptible mice: an effect mimicked by injection of sialokinins, but not demonstrated in flavivirus resistant mice.

Culex pipiens and Aedes aegypti mosquitoes were fed on C3H/HeJ mice and systemic cytokine production was quantified from stimulated lymphocytes harvested four to ten days after feeding. Mosquito feeding on C3H/HeJ mice significantly down regulated IFN gamma production seven to ten days post feeding by Cx. pipiens and seven days after Ae aegypti feeding. Th2 cytokines, IL-4 and IL-10, were significantly up regulated 4-7 days after Cx. pipiens and Ae. aegypti feeding. The immunosuppressive effect of Cx. pipiens feeding on systemic cytokine production was not evident in congenic flavivirus resistant (C3H/RV) mice, as systemic IFN gamma and IL-2 were significantly up regulated at days 7 and 10, correlating with a significant decrease in IL-4 10 days after feeding by Cx. pipiens mosquitoes. Inoculation of 5-1000 ng of sialokinin-I into C3H/HeJ mice mimicked the effect of Ae. aegypti feeding by down regulating Th1 cytokines and significantly up regulating Th2 cytokines four days post inoculation. Injections of sialokinin-II resulted in only moderate effects on IFN gamma and IL-4 production seven and ten days after injection. Thus natural feeding by two arbovirus vectors had a profound T cell modulatory effect in vivo in virus susceptible animals which was not demonstrated in the flavivirus resistant host. Moreover, sialokinin-I and sialokinin-II mimicked the effect of mosquito feeding by modulating the host T cell response. These results may lend new insight into specific aspects of the role of the mosquito vector in potentiating virus transmission in the mammalian host.