Splenic anti-inflammatory reflex in immune tolerance

The injection of repeated doses of lipopolysaccharide (LPS) results in attenuation of the immune response, which is an important mechanism to prevent deleterious long-term excessive inflammation. Brain-mediated mechanisms are involved in this endogenous anti-inflammatory effect, but nothing is known about the putative role of the splenic anti-inflammatory reflex (which has recently been described as a powerful mechanism involved in the suppression of immune response) during immune tolerance. Therefore, we tested the hypothesis that endotoxin tolerance is at least in part mediated by the splenic anti-inflammatory reflex. Body core temperature (Tb) was measured in rats previously submitted to splenectomy. Immune tolerance was induced by means of five consecutive LPS (100 mu g/kg) intraperitoneal injections at 24-h intervals. In sham operated rats, we observed a significant reduction of the febrile response to repeated administration of LPS, which was not altered in rats submitted to splenectomy. Moreover, plasma pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6] and prostaglanding E-2 (PGE(2)) surges besides preoptic PGE(2) levels were observed after the first LPS administration but not in tolerant animals, and this pattern was kept the same in splenectomized rats. These data are consistent with the notion that the splenic anti-inflammatory reflex does not modulate immune tolerance in rats.