RESUMO
OBJECTIVE: Pro-inflammatory cytokines play a critical role in the pathogenesis of RA. A natural oxidant, TauCl exerts anti-inflammatory activities. Here, the effects of Tau and TauCl on key pro-inflammatory cytokines--IL-1beta, IL-6 and TNF-alpha production by LPS-triggered peripheral blood mononuclear cells (PBMCs) isolated from RA and OA patients and healthy blood donors--were examined. METHODS: PBMCs were stimulated with LPS (24 h) in the presence of Tau or TauCl (200-400 microM). Cytokine production was measured in culture supernatants (secreted) and cells lysates (cell-associated) using specific ELISAs. RESULTS: Production of the secretedforms of IL-1beta and IL-6 was inhibited by TauCl with IC50 approximately equal to 250 microM and 300-400 microM respectively, in all investigated groups. In all cultures of PBMCs TauCl raised the TNF-alpha production at the low concentration (200 mM), while at the higher concentration (400 microM) either reduced it (55% of RA, 70% of OA patients and 55% of healthy donors) or exerted no effect (remainder of patients). Interestingly, Tau did not significantly affect any cytokine production. CONCLUSION: TauCl at high concentrations down-regulates pro-inflammatory cytokine production. However, the impact of TauCl on TNF-alpha production by PBMCs from RA is more limited than in cells isolated from OA patients.
