MACROPHAGE INFLAMMATORY PROTEIN-2 PREDICTS ACUTE LUNG INJURY IN ENDOTOXEMIA

Background: Proinflammatory mediators that include tumor necrosis fact or-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) and anti-inflammatory mediators such as interleukin-10 (IL-10) modulate t he immune response to endotoxemia. IL-10 downregulates the production of TNF-alpha and MIP-2, Acute lung injury may occur secondary to neutr ophil chemotaxis mediated by chemokine MIP-2, We studied the temporal relationship of TNF-alpha:, MIP-2, and IL-10 in rat endotoxemia and co rrelation of MIP-2 concentrations with acute lung injury, Methods: Ten ventilated rats were randomized to receive an intravenous infusion of 2 mg/kg Escherichia coil lipopolysaccharide (n = 6) or saline placebo (n = 4), Blood pressure was continuously monitored and arterial blood was obtained for lactate, blood gas, TNF-alpha, IL-10, and MIP-2 meas urements at baseline, 2, 4, and 5.5 hours after LPS or saline infusion , Results: Endotoxemia resulted in hypotension, lactic acidemia, and i ncreased alveolar-arterial oxygen gradient (A-a O-2 gradient) compared with the placebo group, TNF-alpha, MIP-2, and IL-10 levels were incre ased 2 hours after endotoxemia, Subsequently, TNF-alpha levels decline d while IL-10 and MIP-2 levels remained elevated. Control rats had no significant increase in cytokine production at any time point. MIP-2 c oncentrations correlated with A-a O-2 gradient, an indicator of lung i njury (r = 0.56, p < 0.001), Conclusions: MIP-2, possibly released by TNF-alpha stimulation of macrophages, is associated with acute lung in jury possibly by inducing neutrophil chemotaxis, IL-10 may exert its c ounter-inflammatory response by inhibiting the release of TNF-alpha in endotoxemia.