Effect of lisofylline and pentoxifylline on the bacterial-stimulated production of TNF-α, IL-1β, and IL-10 by human leukocytes

The present study concerns the effect of the xanthine-derivates lisofylline (LSF) and pentoxifylline (PTX) on the production of pro-inflammatory cytoldnes TNF and IL-1β and the de-activating cytokine IL-10 by human leukocytes during stimulation with LPS, heat-killed Gram-negative bacteria (GNB) or Gram-positive bacteria (GPB). The production of TNF and IL-1β by leukocytes stimulated with LPS, H. influenzae type b or S. pneumoniae was inhibited by both drugs. The production of IL-10 by leukocytes stimulated with LPS and Hib was inhibited by both xanthine-derivates only at 48 h. However, incubation of leukocytes with S. pneumoniae in the presence of LSF or PTX stimulated the production of IL-10 about four-and two-fold at 24 and 48 h, respectively. In all instances, 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 leukocytes are stimulated by GPB or GNB.