Am. J. Respir. Crit. Care Med., Volume 164, Number 10, November 2001, 1933-1938

Induction of Heme-oxygenase-1 Prevents the Systemic Responses to Hemorrhagic Shock

FABIENNE TAMION, VINCENT RICHARD, GUY BONMARCHAND, JACKY LEROY, JEAN-PIERRE LEBRETON, and CHRISTIAN THUILLEZ

INSERM E9920, IFRMP ² 3 and Service de Réanimation Médicale, Rouen University Hospital, Rouen, France

Oxidant-mediated reperfusion injury of the gut is a major contributor of the systemic inflammatory response in hemorrhagic shock. Recent studies have suggested that heme-oxygenase-1 (HO-1) represents an endogenous protective mechanism against oxidant stress. We assessed whether HO-1 induction modulates the synthesis of tumor necrosis factor- (TNF-) in hemorrhagic shock. In rats submitted to hemorrhagic shock, pretreatment with hemoglobin (Hb) increased HO-1 mRNA expression in macrophages. This increased expression was associated with a decreased expression of TNF- mRNA, as well as decreased plasma concentrations of TNF-. These effects of Hb were reduced by the HO-1 inhibitor tin-protoporphyrin (Sn-PP 20 µmol/kg), while Sn-PP had no effect in the absence of Hb. In parallel, Hb pretreatment reduced pulmonary edema, vascular injury, and increased mesenteric blood flow, and these effects were reduced by Sn-PP. Thus, induction of HO-1 is protective in hemorrhagic shock, possibly through its antioxidant properties. Interventions that induce HO-1 may be beneficial in the treatment of shock states, leading to a reduced systemic inflammatory response.

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