Effects of anti-interleukin 6 on inflammatory responses during murine septic peritonitis

Interleukin (IL)-6 has a limited role in the pathogenesis of the acute systemic inflammatory response syndrome elicited by bolus administration of bacteria or bacterial products. We sought to determine the role of IL-6 in septic peritonitis induced by cecal ligation and puncture (CLP). CLP led to a rapid and sustained induction of IL-6 in plasma and organ homogenates. Pretreatment (-2 h) with an anti-IL-6 mAb (1 mg) resulted in higher plasma and hepatic levels of tumor necrosis factor (TNF), as well as higher plasma concentrations of soluble TNF receptors and IL-10, while attenuating the acute phase protein response. Administration of anti-IL-6 did not influence survival. These results suggest that IL-6 production during septic peritonitis serves to inhibit the appearance of both agonist and antagonist members of the cytokine network. The importance of IL-6 in mediating the cytokine response to infection may be underestimated in more acute sepsis models.