Interplay of TNF-alpha and IL-10 in regulating oxidative stress in isolated adult cardiac myocytes.

Oxidative stress and inflammation are considered to be important factors in the pathogenesis of congestive heart failure subsequent to myocardial infarction. Endogenous TNF-alpha plays a central role in initiating and sustaining the inflammatory response. IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-alpha. In this study, we tested whether an imbalance of these two contrasting cytokines leads to increased oxidative stress and cardiac myocyte dysfunction. Isolated adult rat cardiac myocytes were exposed to different concentrations of TNF-alpha and IL-10 (1-20 ng/ml) alone or in combination. As a positive control, cells were also exposed to H2O2 (100 microI) to induce oxidative stress. An exposure to TNF-alpha (10 ng/ml) caused a significant decrease in both protein and mRNA for manganese superoxide dismutase and catalase, decreased glutathione peroxidase protein, increased intracellular reactive oxygen species and lipid peroxidation, and caused cell injury as measured by creatine kinase release. IL-10 treatment (10 ng/ml) by itself had no effect on any of these parameters, but it prevented all the above listed changes caused by TNF-alpha. IL-10/TNF-alpha ratio of lower or higher than 1 was less effective in reducing TNF-alpha generated oxidative stress. H2O2 treatment increased oxidative stress and cell injury and TNF-alpha mimicked these effects. This study suggests that a proper balance between IL-10 and TNF-alpha, rather than any of the individual cytokines is of more physiological importance in mediating oxidative-stress-induced cardiac injury.