EFFECT OF LISOFYLLINE AND PENTOXIFYLLINE ON THE BACTERIAL-STIMULATED PRODUCTION OF TNF-ALPHA, IL-1-BETA AND IL-10 BY HUMAN-LEUKOCYTES

The present study concerns the effect of the xanthine derivates lisofy lline (LSF) and pentoxifylline (PTX) on the production of pro-inflamma tory cytokines tumour-necrosis factor-alpha (TNF-alpha) and interleuki n-1 beta (IL-1 beta) and the de-activating cytokine interleukin-10 (IL -10) by human leucocytes during stimulation with lipopolysaccharide (L PS), heat-killed Gram-negative bacteria (GNB) or Gram-positive bacteri a (GPB). The production of TNF-alpha and IL-1 beta by leucocytes stimu lated with LPS, Haemophilus influenzae type b (Hib) or Streptococcus p neumoniae was inhibited by both drugs. The production of IL-IO by leuc ocytes stimulated with LPS and Hib was inhibited by both xanthine deri vates only at 48 hr. However, incubation of leucocytes with S. pneumon iae in the presence of LSF or PTX stimulated the production of IL-IO a bout four- and twofold at 24 hr and 48 hr, respectively. In all instan ces, the extent of inhibition or enhancement of cytokine production by LSF or PTX was equal. The divergent effects of xanthine derivates on the IL-10 production indicate the existence of distinct intracellular pathways depending on whether leucocytes are stimulated by GPB or GNB.