Increased Survival After Cecal Ligation and Puncture in Mice Delivering Interleukin 12: The Role of TH1 and TH2 cells

Author(s): Bayram Kiran, Ümit Zeybek, Akif Turna, Hayati Durmaz, Neslihan Cabioglu, Günnur Deniz

Introduction: Severe injury is associated with depressed immune response. The purpose of this study was to analyze the role of T_H1 and T_H2 cells in the stimulated peripheral blood mononuclear cells and determine the effect of IL-12, a cytokine stimulating T_H1 cell proliferation, when administered to septic mice. Methods: Male Balb/c mice underwent sham operation (group 1) or bacterial peritonitis (group 2) which was induced by cecal ligation and puncture and they were treated with IL-12 (group 3), or with IL-10 (group 4) or with both cytokines intraperitoneally (group 5). The T helper-1 (T_H1) and T helper-2 (T_H2) cells were analyzed following stimulation of peripheral blood mononuclear cells with poly-myristate-acetate (PMA) by measuring the intracytoplasmic expression of interleukin-4 (IL-4) and interferon-γ in CD3+- lymphocytes with flow-cytometry. The survival rates of treated mice were compared with non-treated mice. Results: The number of T_H1-cells in mice with peritonitis (group 2) was significantly lower than those in sham-operated mice (p=0.03). In contrast, the number of T_H2-cells was found to be higher in mice with peritonitis (p=0.001) compared to sham-operated. IL-12-administration restored the number of T_H1 and T_H2 cells to those of sham-operated ones. The survival rate of mice treated by IL-12 was found to be significantly improved compared to non-treated mice (p=0.002). However, IL-10 injection almost neutralized the restoring effect of IL-12 administration by improving the survival rate and the T_H1/T_H2 cell counts. Moreover, IL-10 administration alone resulted in lower survival than that of control and sham-operated group (p=0.002). Conclusions: Changes in the T_H1 and T_H2 cells and/or cytokine balance in peritonitis in mice might induce a shift toward a T_H2 dominant phenotype. Therapies designed to increase the number of T_H1 cells such as IL-12 adminisration might be beneficial in the treatment of severe sepsis after peritonitis whereas IL-10 has a deleterious role in sepsis.