Abstract
Little is known about the potential of immunomodulatory agents to lower tumor necrosis factor-α (TNF-α) synthesis in tissues of nonmonocytic origin. We studied effects of diverse drugs on the formation of immunoreactive TNF-α in the human hepatoma cell lines HepG2 and Hep3B, in which TNF-α production was induced by treatment (3 h incubation periods) with interleukin-1β (IL-1β, 300 pg/ml) or phorbol myristate acetate (PMA, 100 nmol/l). TNF-α production in IL-1β-stimulated or PMA-stimulated hepatocyte cultures was not altered following the addition of dihydrocortisone (≤ 1 μg/ml), dibutyryl-cAMP (db-cAMP, ≤ 100 μmol/l), adenosine (≤ 1 mmol/l), thalidomide (≤ 25 μg/ml), or cyclosporine (≤ 300 ng/ml). TNF-α production was inhibited by taurolidine (≥ 300 μg/ml), but this inhibition was associated with reduced cell viability. Pentoxifylline (1 mg/ml) did not influence PMA-induced TNF-α production, but it augmented IL- 1β-induced TNF-α production. Measurements of TNF-α mRNA by RT-PCR indicated that pentoxifylline exerted its effect posttranscriptionally. Additional studies with PMA-treated human whole blood cultures confirmed that pentoxifylline, db-cAMP, and adenosine reduced TNF-α production by leukocytes. These results provide first evidence to assume cell type-specific effects of immunomodulatory drugs on TFN-α synthesis, which may be relevant with respect to their clinical application.
Originalsprache | Englisch |
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Zeitschrift | Journal of Interferon and Cytokine Research |
Jahrgang | 18 |
Ausgabenummer | 12 |
Seiten (von - bis) | 1069-1075 |
Seitenumfang | 7 |
ISSN | 1079-9907 |
DOIs | |
Publikationsstatus | Veröffentlicht - 1998 |
Strategische Forschungsbereiche und Zentren
- Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)