Macrophage inflammatory protein-2 predicts acute lung injury in endotoxemia.
BACKGROUND
Proinflammatory mediators that include tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) and anti-inflammatory mediators such as interleukin-10 (IL-10) modulate the immune response to endotoxemia. IL-10 downregulates the production of TNF-alpha and MIP-2. Acute lung injury may occur secondary to neutrophil chemotaxis mediated by chemokine MIP-2. We studied the temporal relationship of TNF-alpha, MIP-2, and IL-10 in rat endotoxemia and correlation of MIP-2 concentrations with acute lung injury.


METHODS
Ten ventilated rats were randomized to receive an intravenous infusion of 2 mg/kg Escherichia coli 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 measurements at baseline, 2, 4, and 5.5 hours after LPS or saline infusion.


RESULTS
Endotoxemia resulted in hypotension, lactic acidemia, and increased alveolar-arterial oxygen gradient (A-a O2 gradient) compared with the placebo group. TNF-alpha, MIP-2, and IL-10 levels were increased 2 hours after endotoxemia. Subsequently, TNF-alpha levels declined while IL-10 and MIP-2 levels remained elevated. Control rats had no significant increase in cytokine production at any time point. MIP-2 concentrations correlated with A-a O2 gradient, an indicator of lung injury (r = 0.56, p < 0.001).


CONCLUSIONS
MIP-2, possibly released by TNF-alpha stimulation of macrophages, is associated with acute lung injury possibly by inducing neutrophil chemotaxis. IL-10 may exert its counter-inflammatory response by inhibiting the release of TNF-alpha in endotoxemia.
Kalyanaraman
M
M
Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit 48201, USA.
Heidemann
S M
SM
Sarnaik
A P
AP
D000208:Acute Disease; D000818:Animals; D001784:Blood Gas Analysis; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000097:blood*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000097:blood* / Q000209:etiology; D007022:Hypotension / Q000097:blood / Q000209:etiology; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides; D008171:Lung Diseases / Q000097:blood* / Q000209:etiology; D008297:Male; D015846:Monokines / Q000097:blood*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D008070:Lipopolysaccharides; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10