Objective: To preliminarily study the protective effect of chronic schistosoma japonica (SJ) infestation against sepsis in mice and its mechanism.
Methods: BALB/c male mice were used, and the experiment was divided into three parts. Experiment 1: chronic SJ infestation model was reproduced by SJ cercaria inoculation through abdominal skin for 8 weeks. Twenty mice were randomly grouped into normal group (n=10) and SJ group (n=10). The levels of interleukins (IL-4, IL-10),tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in serum were detected by enzyme linked immunosorbent assay (ELISA). Real-time polymerase chain reaction (PCR) was employed to detect the levels of IL-10 mRNA and TNF-αmRNA in abdominal macrophages. This experiment was meant to evaluate immune state in mice with chronic SJ infestation. Experiment 2: lipopolysaccharide (LPS) was intraperitoneally injected to reproduce sepsis model. Thirty mice were randomly grouped into LPS group (n=15) and SJ-LPS group (n=15). The levels of cytokines were determined by ELISA at 0, 24, 48 and 72 hours after LPS injection. This experiment was meant to detect the effect of chronic SJ infestation in mice during the septic process. Experiment 3: two types of sepsis model were reproduced by cecal ligation and puncture (CLP) and LPS injection, respectively. The survival rate of mice with chronic SJ infestation in 72 hours in either type of sepsis was evaluated.
Results: Experiment 1: compared with normal group [IL-4 (56.32±8.66) ng/L, IL-10 (48.17±7.23) ng/L], chronic SJ infestation showed an increase in serum IL-4 [(151.35±12.24) ng/L] and IL-10 [(133.22±11.09) ng/L, both P<0.05]. Chronic SJ infestation also resulted in an increase in IL-10 mRNA expression (SJ group 4.46±1.82, normal group 1.52±0.60) and inhibited TNF-α mRNA expression (SJ group 1.61±0.93, normal group 2.32±1.03) in abdominal macrophages (both P<0.05), indicating that macrophages could be differentiated into alternative activated macrophages. Experiments 2 and 3 showed that the levels of serum IL-4 and IL-10 were increased at 0 hour after LPS injection, and then gradually decreased in SJ-LPS group, but the levels were still higher than those in LPS group at 72 hours [IL-4 (ng/L): 92.2±7.6 vs. 41.5±4.5; IL-10 (ng/L): 92.1±7.8 vs. 35.6±4.0, both P<0.05]; the levels of TNF-α and IFN-γ were increased at 24 hours, and then decreased in SJ-LPS group, and the levels were lower than those in LPS group at 72 hours [TNF-α (ng/L): 82.9±5.6 vs. 91.5±5.2; IFN-γ (ng/L): 44.1±4.8 vs. 52.6±4.0, both P<0.05]. Therefore, chronic SJ infestation could improve the survival rate of mice with sepsis induced by CLP or LPS (CLP: 80% vs. 20%, LPS: 70% vs. 30%, both P<0.05).
Conclusion: Chronic SJ infestation could elevate anti-inflammatory factors in septic mice, thus ameliorating the survival rate, so it has protective effect on mice with sepsis.