Title | Inhibition of human interleukin-12 production by pentoxifylline. |
Publication Type | Journal Article |
Year of Publication | 1997 |
Authors | Moller DR, Wysocka M, Greenlee BM, Ma X, Wahl L, Trinchieri G, Karp CL |
Journal | Immunology |
Volume | 91 |
Issue | 2 |
Pagination | 197-203 |
Date Published | 1997 Jun |
ISSN | 0019-2805 |
Keywords | Cell 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. |
DOI | 10.1046/j.1365-2567.1997.00246.x |
Alternate Journal | Immunology |
PubMed ID | 9227317 |
PubMed Central ID | PMC1363847 |
Grant List | AI-01223 / AI / NIAID NIH HHS / United States HL-56065 / HL / NHLBI NIH HHS / United States P01 HL 49545 / HL / NHLBI NIH HHS / United States |
Submitted by mam2155 on March 24, 2014 - 4:16pm