IL-10 plays a key role in the regulation of TNF-alfa mRNA expression during dna fragmentation in the nephrotoxicity generated by amphotericin b and cyclosporine

Abstract

Inflammation is considered the most important cause of tissue injury in organs subjected to nephrotoxicity induced by drugs. The mechanism that triggers inflammation and organ injury remains to be elucidated, although different causes have been postulated. Thus, this researchinvestigated whether nephrotoxicity generated by amphotericin B (AmB) and cyclosporine (CsA) depends on the balance of cytokines IL-10 and TNF-α, through the evaluation of DNA fragmentation and gene expression of these cytokines in renal cell lines.The results showed that LPS enhances TNF-α mRNA expression and that TNF-α mRNA significantly decreased in the presence of IL-10. The same profile was observed in response to incubation with AmB and CsA,in which both drugs increased the expression of TNF-α mRNA and IL-10 decreases this expression. Thus, IL-10 can reduce the effects generated by nephrotoxicity caused by AmB and CsAby reducing the production of TNF-α. In this context, these results suggest that therapeutic strategies that induce an increase in IL-10 gene expression may be an alternative to decrease the nephrotoxicity caused by AmB and CsA, as demonstrated by IL-10 that modulates the production and gene expression of the TNF-α mRNA and reduces the fragmentation of the DNA induced by drugs.