The Effect Of Diallyl Trisulfide On IL-18 And IL-10 In Serum Of ALI Mice Induced By Lipopolysaccharide

Objective: Acute lung injury (ALI) that clinically manifests as acute respiratory distress syndrome (ARDS) is a major component of multiple organ dysfunction syndrome (MODS) of various etiologies. ALI is commonly defined as"acute non-cardiogenic edematous lung injury".The pathophysiological pathogenesis of ALI and ARDS is similar, but the severity is different, ARDS is the severe endpoint of ALI. No specific therapy can cure ALI/ARDS, although mechanical ventilation and other methods had been conducted. The disease is devastating in clinic patients and the mortality was reported to be 40%～60%.Diallyl trisulfide (DATS) is the main component of garlic extract. Garlic is allium satirum of Liliaceae (Allium satirum. L). DATS and diallyl disulfide (DADS) are the main effective components in garlic. ZHU guijun et al,the doctor of ICU of the fourth hospital of Hebei Medical University , first systematically investigated the preventive and therapeutic effect of DATS on ALI mice induced by LPS and related mechanisms from protein kinase to transcription factors and the genehexpression of proinflammatory cytokines. This study indicated that DATS could decrease the production of the pro-inflammatory cytokines, example of TNF-αand IL-1β, and pretreatment with DATS may provide a new preventive and therapeutic tool for ALI. IL-18, as a proinflammatory cytokine, can enhances the secretion of TNF-α,IL-1β,IL-8,GM-CSF, and then increases IFN-γ. So IL-18 can be considered as a prognostic factor to severe sepsis. IL-10 is considered as a very important anti-inflammatory cytokine. In this study, we observed the effect of DATS on the inflammatory cytokines(IL-18,IL-10) in serum of LPS-induced ALI mice in order to provide rational experimental evidence for the clinical treatment of ALI/ARDS.Methods: Ninety healthy kun-ming mice were randomly divided into five groups: (1)ALI group: mice were infused LPS (10mg/kg) intraperitoneally; (2)DATS prevention group: mice were infused DATS (30mg/kg) intraperitoneally for 7 days and then received LPS (10mg/kg) injection; (3)DATS treatment group: mice were infused LPS (10mg/kg) intraperitoneally and then received DATS (30mg/kg) injection 30min later; (4)DATS group:mice received DATS (30mg/kg) injection intraperitoneal- ly for 7 days and without LPS injection; (5)Control group: mice were received the same bulk of sodium chloride injection. The histopathology changes of lung tissues at 12h were examined with HE stain lung-biopsy specimen under light microscopy. The levels of IL-18 and IL-10 in the serum were detected with enzyme linked immunosorbent assay (ELISA) at 2h and 6h. Data were presented as x±s and analyzed with ANOVA using SPSS 12.0 statistical program.A level of P < 0.05 was considered to be statistically significant.Result1 The histopathology changes of lung tissueLung gross anatomy: no abnormal histomorphology changes were found in control group and DATS group. In ALI group, the lung was heavy and swelling in dark red color with diffuse spots. The lung parenchymal surface was crumbly and was rich of erythroic edema fluid. The pathological changes were lessened obviously in DATS prevention group compare with that in ALI group. But the histomorphology changes were similar between DATS treatment group and ALI group. Light microscopy: the lung structure including alveolar space and alveolar septum were normal without edema in control group and DATS group. But there were alveolar septum widening, capillary congestion, interstitial and alveolar edema, intra-alveolar hemorrhage, and multiply inflammatory cells infiltration in the lungs of ALI mice. Pretreatment with DATS could significantly alleviate the lung injury of ALI. However, no But no significantly influence was found in DATS treatment group.2 IL-18 level in the serum of miceIn ALI group, the level of IL-18 in the serum increased significantly at 2h(P<0.01 vs control group), and decreased at 6h, but was also higher than that in control group (P<0.01). In DATS prevention group, the concentration of IL-18 in the serum decreased significantly at 2h and 6h(P < 0.01 vs ALI group).However, in DATS treatment group, the level of IL-18 in the serum did not decrease compared with that of ALI group (P>0.05). DATS alone had no influence on the production of IL-18 in the serum (P>0.05 vs control group). These results indicate pretreatment with DATS inhibits IL-18 production in the serum in LPS-induced ALI mice.3 IL-10 level in the serum of miceIn ALI group, the level of IL-10 in the serum increased significantly at 2h and 6h (P<0.01 vs control group). In DATS prevention group, the concentration of IL-10 in the serum was higher than that of ALI group at 2h and 6h obviously (P<0.01 vs ALI group).However, in DATS treatment group, the level of IL-10 in the serum did not increase compared with that of ALI group (P>0.05). There was no significant difference between the DATS group and control group on IL-18 production in the serum in LPS-induced ALI mice (P >0.05).Conclusions1 Pretreatment with DATS could alleviate the degree of pulmonary edema and pulmonary inflammation in LPS-induced ALI mice.2 The IL-18 level in the serum of LPS-induced ALI mice is significantly higher than that of control group, which shows more IL-18 is produced in LPS-induced ALI mice.3 Pretreatment with DATS could inhibit the production of IL-18 in the serum in LPS-induced ALI mice.4 Pretreatment with DATS could increase the production of IL-10 in the serum in LPS-induced ALI mice.5 It could be concluded that DATS has a beneficial protective function on ALI induced by LPS through regulating the contents of IL-18 and IL-10, and ameliorating the lung pathological change of ALI mice respectively.