change in content of multiple cytokines in the serum of mods mice and its relationship with disease progression

Objective　To analyze the changes in multiple cytokines in serum in the development of zymosan-induced multiple organ dysfunction syndrome (MODS) in mice, and explore its relationship with deterioration of MODS. Methods　MODS model of C57BL/6 mice was reproduced by intraperitoneal injection of zymosan. Organ function and mortality rate were observed, and serum levels of several cytokines were measured using ELISA at the different stages of the development of MODS. Results　 Serum levels of alanine aminotransferase, blood urea nitrogen, creatinine and creatine kinase were enhanced and maintained at a high level during the period of 12h to 2d after the challenge with zymosan, and then lowered to normal levels after 5-7d, but they were increased again at 10-12d (P<0.05 or P<0.01). The occurrence of organ dysfunction was found to correspond to peaks of death at 1-2d and 10-12d following zymosan challenge. Serum levels of multiple cytokines changed sequentially corresponding to deterioration of MODS. TNF and IL-1 levels were elevated at 6-12h, HMGB1 content was increased 1d later, and IL-10 concentration was increased at 5d after zymosan administration. IL-2 and IL-12 levels showed a decreasing tendency during the development of MODS. At the late stage of MODS, serum levels of both pro-inflammatory and anti-inflammatory mediators were significantly elevated, while IL-2 and IL-12 levels were dramatically lowered. Conclusions　In the progression of zymosan-induced mouse MODS, serum levels of multiple pro-inflammatory and anti-inflammatory mediators may present sequential changes, showing dominant immunoactivation at early stage and obvious immunosuppression at late stage, which may be associated with the degree of severity of MODS. Dynamical investigation of the changes in serum cytokines is helpful to judge the development of MODS, and corresponding therapeutic strategies could be taken. DOI: 10.11855/j.issn.0577-7402.2014.07.03