Extrinsic allergic alveolitis: inhibitory effects of pentoxifylline on cytokine production by alveolar macrophages.

BACKGROUND: Pentoxifylline is a well-established drug with hemorheologic properties. Various evidence suggests an additional therapeutic potential in regard to inflammation and immunomodulation. Extrinsic allergic alveolitis (EAA) is a granulomatous disease that is driven by T-cell and alveolar macrophage (AM)-derived cytokines. OBJECTIVE: To investigate the effects of pentoxifylline on the production of tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, IL-6, IL-8, IL-10, and the soluble TNF receptors (sTNFR1 and sTNFR2) from AMs in EAA compared with dexamethasone. METHODS: The AMs from 9 patients with EAA were cultured for 24 hours with RPMI medium alone or lipopolysaccharide (LPS) (100 ng/mL) and with pentoxifylline at concentrations of 0.01, 0.1, and 1 mmol/L or 0.1-mmol/L dexamethasone. Cytokines in the culture supernatants were analyzed by enzyme-linked immunosorbent assay. RESULTS: Pentoxifylline induced a dose-dependent suppression of spontaneous TNF-alpha and IL-10 release from AMs in EAA. The spontaneous production of other cytokines was unaffected by pentoxifylline at all tested concentrations. Dexamethasone inhibited significantly only the spontaneous release of TNF-alpha. Pentoxifylline and dexamethasone also inhibited the LPS-stimulated production of all cytokines except IL-1beta and sTNFR1. CONCLUSION: Our results may be the basis for clinical trials to evaluate the role of pentoxifylline as an immunotherapeutic agent in the treatment of EAA.