Generation of Pro-inflammatory and Anti-inflammatory Cytokines in the Gut in Zymosan-induced Peritonitis

In major systemic inflammation such as severe peritonitis, various pro-inflammatory cytokines, such as TNF-α, IL-1/) and IL-6, play important roles in the development of multiple organ dysfunction syndrome (MODS). The purpose of this study was to investigate the outflow of pro-inflammatory and anti-inflammatory cytokines from the efferent mesenteric lymphatic vessels under peritonitis. Mesenteric lymph samples were collected from adult male rats at 2, 4, 6, 8 and 10 hr after an intraperitoneal injection of zymosan at a dosage of 0.1 mg/g (non-lethal dose) or 0.5 mg/g (lethal dose). Blood samples were obtained at 10 hr after zymosan administration. The amounts of drained TNF-α and IL-6 in the lymph peaked at 2-4 hr and 4-8 hr after zymosan administration, respectively. The amounts of drained IL-10 in the lymph gradually increased until 10 hr. The amounts of drained TNF-αand IL-10 in the mesenteric lymph were significantly correlated with the dosage of zymosan. In conclusion, under intraperitoneal inflammation, pro-inflammatory cytokines (TNF-αand IL-6) increased in the mesenteric lymph and were drained into circulation. IL-10, one of the anti-inflammatory cytokines, also increased in the mesenteric lymph after several hours' delay and its increase was remarkable in severe inflammations. These findings suggested that the gut might be one of the pro-inflammatory and anti-inflammatory cytokine-generating organs under peritonitis. The lymph-drained amounts of each cytokine under peritonitis are considered to differ with the time or severity of inflammation, which may cause different conditions in patients due to the imbalance of pro-inflammatory and anti-inflammatory cytokines.This work was supported by a Grant-in Aid from the Ministry of Education, Science and Culture