Anti-inflammatory effects of inosine in human monocytes, neutrophils and epithelial cells in vitro

Inosine is an endogenous purine, which has been recently shown to exert imm unomodulatory, and-inflammatory and anti-shock effects in rodent experiment al systems. Some of these actions may be related to partial adenosine. rece ptor agonistic effects. It has not been investigated previously whether ino sine exerts similar immunomodulatory or antiinflammatory effects in human c ells or enzymes. Here we investigated the effects of inosine on the activat ion of human monocytes, neutrophils and epithelial cells in vitro. Furtherm ore, using a human inosine-5'-monophosphate dehydrogenase (IMPDH) enzyme, w e examined the potential effects of inosine on the activity of IMPDH, an en zyme involved in the regulation of certain inflammatory/immune processes. T umor necrosis factor a (TNF-a) production of bacterial lipopolysaccharide. (LPS) stimulated whole blood was used as an indicator of human monocyte act ivation. The response was dose-dependently, partially suppressed in the pre sence of inosine. Inosine. exerted a dose-dependent and, at the highest dos e (3 mM), complete inhibition of the ability of human neutrophils activated with N-formyl-methionyl-leucylphenylalanine. (fMLP) to induce cytochrome C reduction in vitro. In the human colon cancer cell line HT-29, inosine dos e-dependently attenuated the production of IL-8. Inosine failed to affect t he activity of IMPDH. Taken together, we conclude that inosine exerts anti- inflammatory effects in many human cell types. Further studies need to esta blish whether inosine supplementation exerts anti-inflammatory effects in h uman beings.