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

We investigated the role of interleukin-1 in the induction of a Ca²⁺-independent nitric oxide (NO) synthase by bacterial endotoxin in vivo. In anaesthetized rats, pretreatment with interleukin-1 receptor antagonist (interleukin-1_ra; 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 Ca²⁺-inependent NO synthase activity in the lung and reduced the contractions to noradrenaline in the thoracic aorta ex vivo. Treatment with interleukin-1_ra 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.