title: Exogenous human recombinant interleukin-10 attenuates hindlimb ischemia-reperfusion injury.
abstract: Proinflammatory cytokines have been found to mediate part of the local and distant organ injury after ischemia and reperfusion (I/R). 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 micrograms i.v., n = 10), SHAM (n = 4); or SHAM+IL-10 (10 micrograms i.v., 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 99Tc pyrophosphate while soleus muscle capillary permeability, and lung capillary permeability were assessed by uptake of 125I-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.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville 32610-0286, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Engles
authors.forename: T S
authors.initials: TS
authors.lastname: Huber
authors.forename: D S
authors.initials: DS
authors.lastname: Zander
authors.forename: P J
authors.initials: PJ
authors.lastname: Hess
authors.forename: M B
authors.initials: MB
authors.lastname: Welborn
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: J M
authors.initials: JM
authors.lastname: Seeger
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10