Differential effects of pentoxifylline and interleukin-10 on production of tumor necrosis factor and inducible nitric oxide synthase by murine macrophages.
The abilities of pentoxifylline and recombinant interleukin-10 (rIL-10) to inhibit tumor necrosis factor (TNF) and inducible nitric oxide synthase (iNOS) production in RAW 264.7 murine macrophages were compared. Pentoxifylline consistently inhibited the accumulation of both TNF and iNOS in a dose-dependent manner whether the stimulus was bacterial lipopolysaccharide (LPS), recombinant interferon-gamma (rIFN-gamma), or LPS plus rIFN-gamma. Similarly, rIL-10 consistently reduced TNF production by cells stimulated with LPS, rIFN-gamma, or LPS plus rIFN-gamma. However, rIL-10 weakly inhibited LPS-induced iNOS production but failed to block (and often augmented) rIFN-gamma-induced iNOS production. Combinations of pentoxifylline and rIL-10 led to additive or synergistic inhibition of TNF but not iNOS production; in fact, rIL-10 appeared to interfere with the ability of pentoxifylline to block iNOS accumulation. These data suggest that combinations of antiinflammatory agents may have unanticipated effects on inflammatory mediator production.
Loftis
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LL
Department of Pediatrics, University of Tennessee, Memphis 38103, USA.
Meals
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EA
English
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BK
D000818:Animals; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D010431:Pentoxifylline