Studies have suggested the pivotal role of T helper type 1 (Th1) -related cytokines on the outcome of hepatitis C virus (HCV) infection. Nevertheless, the role of different interleukin-17 (IL-17) -secreting T cells on chronic hepatitis C (CHC) is less clear. Here, the in vivo IL-1β, IL-6, and IL-17 levels were positively correlated with both alanine transaminase (ALT) levels and hepatic lesions. When compared with the control group, CHC patients showed a lower proportion of IL-17-secreting (CD4 and CD8 ) T cells capable of simultaneously producing IL-21. Moreover, the percentage of IL-10-secreting Th17 cells was also lower in CHC patients. Notably, advanced liver lesions were observed among those patients with lower percentage levels of IL-17-producing T cells positive for IL-21, interferon-γ (IFN-γ) and IL-10. In contrast, the severity of hepatic damage was associated with peripheral single IL-17 T cells. The percentage of IL-17 IL-21 IFN-γ (CD4 and CD8 ) T-cell phenotypes was positively associated with plasma CD14 levels. Finally, elevated levels of circulating CD14 were detected among CHC patients with extensive liver damage. In summary, although preliminary, our results suggest that a balance between different IL-17-producing T cells, associated with peripheral levels of CD14, may be a progress marker for liver disease in chronically HCV-infected patients.
Background
Obesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4+T‐cell subsets from lean, overweight and obese AA patients.
Methods
Mononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4+T‐cell subsets and type 1 regulatory B cells (Br1) was determined by cytometry. The effect of obese‐related leptin dose on cytokine production and Treg cell function in AA‐derived CD4+ T cell cultures was evaluated by ELISA and 3H thymidine uptake, respectively. Leptin levels were quantified in the plasma by ELISA. According to the BMI, patients were stratified as lean, overweight and obese.
Results
AA severity, mainly among obese patients, was associated with an expansion of hybrid Th2/Th17 and Th17‐like cells rather than classic Th2‐like cells. On the other hand, the frequencies of Th1‐like, Br1 cells and regulatory CD4+ T‐cell subsets were lower in patients with severe AA. While percentages of the hybrid Th2/Th17 phenotype and Th17‐like cells positively correlated with leptin levels, the frequencies of regulatory CD4+ T‐cell subsets and Br1 cells negatively correlated with this adipokine. Interestingly, the obesity‐related leptin dose not only elevated Th2 and Th17 cytokine levels, but also directly reduced the Treg function in CD4+ T cell cultures from lean AA patients.
Conclusion
In summary, our results indicated that obesity might increase AA severity by favoring the expansion of Th17‐like and Th2/Th17 cells and decreasing regulatory CD4+T cell subsets, being adverse effects probably mediated by leptin overproduction.
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