Terbutaline prevents circulatory failure and mitigates mortality in rodents with endotoxemia

Septic shock is characterized by a decrease in systemic vascular resistance . Nevertheless, regional increases in vascular resistance can occur that ma y predispose mammals to organ dysfunction, including the acute respiratory distress syndrome. In the host infected by endotoxin (lipopolysaccharide, L PS), the expression and release of proinflammatory tumor necrosis factor-al pha (TNF alpha) rapidly increases, and this cytokine production is regulate d by agents elevating cyclic AMP. In this report, we present evidence that terbutaline, a beta(2)-agonist, inhibits TNF alpha production and enhances interleukin-10 (IL-10) release in the anesthetized rat treated with LPS, In addition, an overproduction of nitric oxide (NO, examined by its metabolit es nitrite/nitrate) by inducible NO synthase (iNOS, examined by western blo t analysis) is attenuated by pretreatment of LPS rats with terbutaline. Ove rall, pretreatment of rats with terbutaline attenuates the delayed hypotens ion and prevents vascular hyporeactivity to norepinephrine. In addition, pr etreatment of mice with terbutaline also improves the survival in a model o f severe endotoxemia. The infiltration of polymorphonuclear neutrophils int o organs (e.g., lung and liver) from the surviving LPS mice treated with te rbutaline was reduced almost to that seen in the normal controls. These fin dings suggest that the inhibition of TNF alpha and NO (via iNOS) production as well as the increment of IL-10 production contribute to the beneficial effect of terbutaline in animals with endotoxic shock.