Inhibition of human interleukin-12 production by pentoxifylline

D. R. Moller, M. Wysocka, B. M. Greenlee, X. Ma, L. Wahl, G. Trinchieri, C. L. Karp

Research output: Contribution to journalArticlepeer-review

Abstract

Pharmacological control of interleukin-12 (IL-12) production may be a key therapeutic strategy for modulating immunological diseases dominated by type-1 cytokine responses. In this study, we investigated the effects of pentoxifylline on the production of IL-12 by human blood mononuclear cells and primary human monocytes stimulated with heat-killed Staphylococcus aureus Cowan strain 1 (SAC) or lipopolysaccharide (LPS). Pentoxifylline potently suppressed production of IL-12 in a concentration-dependent manner. In these same experiments, tumour necrosis factor-α (TNF-α) production was inhibited and IL-10 and prostaglandin E2 (PGE2) production was enhanced by treatment with pentoxifylline. Suppression of IL-12 production by pentoxifylline was found to be independent of several known endogenous inhibitors of IL-12, such as IL-10, transforming growth factor-β (TGF-β), IL-4 and PGE2. RNase protection assays revealed that pentoxifylline inhibited accumulation of both IL-12 p40 and p35 mRNA, suggesting a predominant mRNA locus for pentoxifylline-induced IL-12 inhibition. Low levels of pentoxifylline added to the suppression of IL-12 production by suboptimal inhibiting doses of dexamethasone, suggesting that this drug combination may have therapeutic utility. These results provide a firm rationale for the use of pentoxifylline in clinical trials of immunological disorders characterized by inappropriate type-1 immune responses.

Original languageEnglish (US)
Pages (from-to)197-203
Number of pages7
JournalImmunology
Volume91
Issue number2
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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