Modulation of LPS-, PHA- and M-tuberculosis-mediated cytokine production by pentoxifylline and thalidomide

Pentoxifylline and thalidomide have been used to downregulate the productio n of TNF-alpha in several disease entities including mycobacterial infectio ns and autoimmune disorders. These drugs inhibit the production of TNF-alph a by different mechanisms, but little is known about possible synergism and modulation of other cytokines, Pentoxifylline and thalidomide inhibited the in vitro stimulated production of TNF-alpha, IL-1 beta and IFN-gamma in blood mononuclear cells. No signi ficant modulation of antiinflammatory cytokines was found. When used togeth er, these agents demonstrated additive inhibition, but no synergism. Modula tion of cytokine response was similar when different stimuli were used, inc luding ill, tuberculosis in tuberculin-positive individuals. Therefore, the balance between efficacy and toxicity may be more favourable when pentoxifylline and thalidomide are used together instead of either dr ug alone. Clinical studies are needed to establish this advantage when anti -cytokine strategies are considered.