Exogenous human recombinant interleukin-10 attenuates hindlimb ischemia-reperfusion injury

Proinflammatory cytokines have been found to mediate part of the local and distant organ injury after ischemia and reperfusion (IIR). The anti-inflammatory cytokine interleukin - 10 (IL-10) inhibits both TNF - alpha and IL-1, and we hypothesized that exogenous human IL-10 may decrease lung and soleus muscle injury after hindlimb I/R. Male Sprague-Dawley rats were randomly assigned to I/R (n = 10); I/R + IL-10 (10 mu g iv, n = 10), SHAM (n = 4); or SHAM + IL-10 (10 mu g iv, n = 4). Bilateral hindlimb ischemia was produced by tourniquet occlusion for 4 hr and all animals were sacrificed after 4 hr of reperfusion or at comparable times for the SHAMs. Soleus muscle cellular injury was determined by uptake of Tc-99 pyrophosphate while soleus muscle capillary permeability, and lung capillary permeability were assessed by uptake of I-125-labeled albumin. Soleus muscle and lung neutrophil infiltration were measured with the myeloperoxidase assay. Serum samples were assessed for TNF - alpha production with the WEHI bioassay. Hindlimb I/R caused significant soleus muscle cellular injury, soleus muscle capillary injury, lung capillary injury, and lung neutrophil infiltration. Pretreatment with exogenous IL-10 significantly reduced soleus muscle capillary permeability and also reduced soleus muscle cellular injury, but not to a statistically significant degree. IL-10 administration also reduced pulmonary capillary permeability despite significantly increased lung neutrophil infiltration. Elevated TNF - alpha levels were found in 66% (4/6) rats in the I/R group versus 30% (3/10) rats in the I/R + IL-10 group. Exogenous IL-10 attenuates both local and distant organ injury after hindlimb I/R potentially independent of neutrophil infiltration. (C) 1997 Academic Press.