Inhibitory Effects of Actinomycin-D and Pentoxifylline on the Production of IL-1alpha and TNF-alpha by Human Cord and Adult Blood Mononuclear Cells

ABSTRACT

PURPOSE: An area of intense intrest is assessment of new therapeutic modalities that regulate the inflammatory response in acute bacterial infection is proving to be an area of interest these days. So we conducted this study to compare the inhibitory effects of actinomycin-D and pentoxifylline on the production of IL-lalpha and TNF-alpha from cord blood mononuclear cells (MC) to those from adult blood MC stimulated with S. aureus toxic shock syndrome toxin (TSST)-1 and E. coli lipopolysaccharide (LPS). METHODS: Cord and adult blood MC were isolated by differential centrifugation on Ficoll-Hypaque gradients. Each mononuclear cells were incubated with TSST-1 (2 microgram/ml) or LPS (0.2 microgram/ml), simultaneously with various concentrations of actinomycin-D or pentoxifylline added for inhibition. Concentration of interleukin-1alpha (IL-lalpha) and tumor necrosis factor-alpha (TNF-alpha) were measured by means of ELISA. RESULTS: In comparison with each inhibitory drug, actinomycin-D showed more potent inhibitory effects on the production of IL-1alpha and TNF-alpha from adult and cord blood MC stimulated by TSST-1 and LPS, than pentoxifylline (P<0.05). There was no difference between adult and cord blood MC. In comparison with each stimulator, inhibition of TSST-1 induced cytokines production with actinomycin-D was greater than pentoxifylline, in contrast to inhibition of LPS induced cytokines production with pentoxifylline which was greater than actinomycin-D in adult blood MC (P<0.05). CONCLUSION: Proinflammatory cytokine production in cord and adult blood MC were inhibited by each drug in the same manner except, the inhibition of pentoxifylline for LPS in cord blood MC. So it is possible that these drugs can be used to modulate or suppress excessive proinflammatory cytokine production in acute bacterial infection.