Objectives: Pentoxifylline (POF) is a well established drug with haemorrheological properties. Various evidence suggests an additional therapeutic potential in regard to inflammation and immunomodulation. Extrinsic allergic alveolitis (EAA) is a granulomatous disease which is driven by T cell and alveolar macrophage (AM) derived cytokines. To investigate the effects of POF 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 AM in EAA, also in comparison with dexamethasone (DEX).
Methods: AM from 9 patients with EAA were cultured for 24 h with 10% RPMI medium alone, or with lipopolysaccharide (LPS, 100 micro g/L), and with POF at concentrations of 0.01 mmol/L, 0.1 mmol/L and 1 mmol/L, or with 0.1 mmol/L DEX. Cytokines in the culture supernatants were analysed by ELISA.
Results: POF induced a dose dependent suppression of spontaneous TNFalpha and IL-10 release from AM in EAA (P < 0.001 and P < 0.05). The spontaneous production of other cytokines was unaffected by POF at all tested concentrations. DEX inhibited only the spontaneous release of TNFalpha significantly (P < 0.05). POF and DEX also inhibited the LPS-stimulated production of all cytokines except of IL-1beta and sTNFR1 (P < 0.001 or P < 0.01 or P < 0.05).
Conclusion: Our results may be the basis for clinical trials to evaluate the role of POF as an immunotherapeutic agent in the treatment of EAA.