Interleukin-1 contributes to the induction of nitric oxide synthase by endotoxin in vivo.

Overview

We investigated the role of interleukin-1 in the induction of a Ca(2+)-independent nitric oxide (NO) synthase by bacterial endotoxin in vivo. In anaesthetized rats, pretreatment with interleukin-1 receptor antagonist (interleukin-1ra; 16 mg kg-1 i.v., followed by an infusion of 2.4 mg kg-1 h-1) ameliorated the delayed hypotension and tachycardia in response to endotoxin (2 mg kg-1 i.v.). Endotoxaemia for 3 h induced a Ca(2+)-independent NO synthase activity in the lung and reduced the contractions to noradrenaline in the thoracic aorta ex vivo. Treatment with interleukin-1ra attenuated both the induction of NO synthase in the lung (by 46 +/- 5%) and the endotoxin-induced hyporeactivity to noradrenaline in the aorta. Thus, endogenous interleukin-1 contributes to the induction of NO synthase in response to endotoxin in vivo.