Inhibition of cytokine release from alveolar macrophages in pulmonary sarcoidosis by pentoxifylline: comparison with dexamethasone

Chest. 2003 Oct;124(4):1526-32. doi: 10.1378/chest.124.4.1526.


Study objectives: Pentoxifylline (POF) has been shown to suppress the cytokine production from lipopolysaccharide (LPS)-stimulated monocytes/alveolar macrophages (AMs). Sarcoidosis is a granulomatous disease that is driven by the action of tumor necrosis factor (TNF)-alpha and other proinflammatory cytokines. In this study, we aimed to investigate the effects of POF on the production of TNF-alpha, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, and the soluble TNF receptors (sTNFRs) 1 and 2 from AMs in sarcoidosis, and we also compared them with those of dexamethasone (DEX).

Methods: AMs from 14 patients with sarcoidosis were cultured for 24 h with RPMI medium alone or with LPS (100 ng/mL), and with POF at concentrations of 0.01, 0.1, and 1 mmol/L, or with 0.1 mmol/L DEX. Cytokines in the culture supernatants were analyzed by enzyme-linked immunosorbent assay.

Results: The results showed that POF induced a dose-dependent suppression of the spontaneous TNF-alpha release from AMs in sarcoidosis (p < 0.001), and that the spontaneous release of the other cytokines was unaffected by POF at all tested concentrations, but a trend for the inhibition of IL-10 production was found (p = 0.092). DEX inhibited the spontaneous release of TNF-alpha (p < 0.001), sTNFR2 (p < 0.05), IL-1 beta (p < 0.05), and IL-10 (p < 0.01). POF also suppressed the LPS-stimulated production of these cytokines except for that of sTNFR1. Similar to POF, DEX inhibited the LPS-stimulated production of these cytokines, but not that of sTNFR1 and IL-1 beta.

Conclusions: Compared with DEX, POF may improve therapeutic regimens in patients with sarcoidosis either by sparing or by replacing corticosteroids. However, the precise clinical value of POF in the treatment of sarcoidosis and other lung diseases will have to be determined in further clinical trials.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / metabolism*
  • Dexamethasone / pharmacology*
  • Female
  • Humans
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / immunology*
  • Male
  • Middle Aged
  • Pentoxifylline / pharmacology*
  • Sarcoidosis, Pulmonary / immunology*


  • Anti-Inflammatory Agents
  • Cytokines
  • Dexamethasone
  • Pentoxifylline