Inhibitory Effects of Dexamethasone on Production IL-1alpha and TNF-alpha in Peripheral Blood Mononuclear Cells

ABSTRACT

PURPOSE: IL-1alpha and TNF-alpha have a seminal role in the intial events of inflammation. An area of intense interest is the assessment of new therapeutic modalities that regulate inflammatory response in acute bacterial infection. We conducted this study to compare the inhibitory effects of dexamethasone on the secretion of proinflammatory cytokines, such as IL-lalpha and TNF-alpha from cord blood mononuclear cells(MC) to those of adult blood MC during stimulation with S. aureus TSST-1 and E. coli LPS. METHODS: MC were isolated by differential centrifugation on Ficoll-Hypaque gradients. Each MC were incubated with TSST-1(2ug/ml) or LPS(0.2ug/ml), with various concentrations of dexamethasone for 72hr. And the other MC were incubated with TSST-1 or LPS, using the same concentration of dexamethasone, which was added 4hr before or simultaneously or 4hr, 24hr, 48hr after the stimulation. Concentration of IL-1alpha and TNF-alpha was measured by ELISA kit. RESULTS: Dexamethasone showed significant inhibitory effects on secretion of IL-1alpha and TNF-alpha. In comparison with both cytokines, secretion of IL-1alpha was suppressed more severely than TNF-alpha. In comparison with each stimulators, inhibition of TSST-1 induced cytokines production was greater than LPS. There was no difference between adult and cord blood MC. When dexamethasone was added to MC 4hr before the stimulation, it had the best inhibitory effects on the production of proinflammatory cytokines. CONCLUSION: Proinflammatory cytokine production in cord and adult blood MC were inhibited by dexamethasone in a dose-dependent manner. Early treatment of dexamethasone is more effective and can be used for modulating or suppressing excessive proinflammatory cytokine production in acute bacterial infection.