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Inhibition of human interleukin-12 production by pentoxifylline.

TitleInhibition of human interleukin-12 production by pentoxifylline.
Publication TypeJournal Article
Year of Publication1997
AuthorsMoller DR, Wysocka M, Greenlee BM, Ma X, Wahl L, Trinchieri G, Karp CL
JournalImmunology
Volume91
Issue2
Pagination197-203
Date Published1997 Jun
ISSN0019-2805
KeywordsCell Culture Techniques, Dexamethasone, Dose-Response Relationship, Drug, Humans, Indomethacin, Interleukin-10, Interleukin-12, Leukocytes, Mononuclear, Monocytes, Pentoxifylline, RNA, Messenger, Transforming Growth Factor beta
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 I (SAC) or lipopolysaccharide (LPS). Pentoxifylline potently suppressed production of IL-12 in a concentration-dependent manner. In these same experiments, tumour necrosis factor-alpha (TNF-alpha) 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-beta (TGF-beta), 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.

DOI10.1046/j.1365-2567.1997.00246.x
Alternate JournalImmunology
PubMed ID9227317
PubMed Central IDPMC1363847
Grant ListAI-01223 / AI / NIAID NIH HHS / United States
HL-56065 / HL / NHLBI NIH HHS / United States
P01 HL 49545 / HL / NHLBI NIH HHS / United States

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