Cardioprotective actions of endogenous IL-10 are independent of iNOS.
Myocardial ischemia-reperfusion (I/R) is a well-known stimulus for acute inflammatory responses that promote cell death and impair pump function. Interleukin-10 (IL-10) is an endogenous, potent anti-inflammatory cytokine. Recently, it has been proposed that IL-10 inhibits inducible nitric oxide synthase (iNOS) activity after myocardial I/R and consequently exerts cardioprotective effects. However, whether this actually occurs remains unclear. To test this hypothesis, we utilized iNOS-deficient (-/-), IL-10 -/-, and IL-10/iNOS -/- mice to examine the potential mechanism of IL-10-mediated cardioprotection after myocardial I/R. Wild-type, iNOS -/-, IL-10 -/-, and IL-10/iNOS -/- mice were subjected to in vivo myocardial ischemia (30 min) and reperfusion (24 h). Deficiency of iNOS alone did not significantly alter the extent of myocardial necrosis compared with wild-type mice. We found that deficiency of IL-10 resulted in a significantly (P < 0.05) larger infarct size than that in wild-type hearts. Interestingly, deficiency of both IL-10 and iNOS yielded significantly (P < 0.01) larger myocardial infarct sizes compared with wild-type animals. Histological examination of myocardial tissue samples revealed augmented neutrophil infiltration into the I/R myocardium of IL-10 -/- and IL-10/iNOS -/- mice compared with hearts of wild-type mice. These results demonstrate that 1) deficiency of endogenous IL-10 exacerbates myocardial injury after I/R; 2) the cardioprotective effects of IL-10 are not dependent on the presence or absence of iNOS; and 3) deficiency of IL-10 enhances the infiltration of neutrophils into the myocardium after I/R.
Jones
S P
SP
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Trocha
S D
SD
Lefer
D J
DJ
D000818:Animals; D006321:Heart / Q000502:physiology*; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D020011:Protective Agents; D012016:Reference Values
D020011:Protective Agents; D016753:Interleukin-10; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse