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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.

Objective: Pentoxifylline (POF) has recently been shown to suppress the cytokine production from lipopolysaccharide (LPS) stimulated monocytes/alveolar macrophages (AM). Sarcoidosis is a granulomatous disease which is driven by the action of tumor necrosis factor (TNF-alpha) and other proinflammatory cytokines. It was investigated that the effects of POF on the production of TNF-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and the soluble TNF-alpha receptors (sTNFR-1 and sTNFR-2) from AM in sarcoidosis, as comparison to dexamethasone (DEX)., Methods: AM from 14 patients with active pulmonary sarcoidosis were cultured for 24 h with RPMI medium alone, or with 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 the spontaneous TNF-alpha release from AM in sarcoidosis (P < 0.001), while the spontaneous release of 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 0.1 mmol/L inhibited the spontaneous release of TNF-alpha, sTNFR-2, IL-1beta and IL-10 (P < 0.001 or < 0.05 or <0.01). POF also suppressed the production of these LPS-stimulated cytokines except of sTNFR-1 (P < 0.05 or < 0.001). Similar to POF, DEX (0.1 mmol/L) inhibited the production of these LPS-stimulated cytokines (P < 0.05 or < 0.001), but not of sTNFR-1 and IL-1beta., Conclusions: Compared with DEX, POF may improve the therapy of sarcoidosis by either sparing or replacing corticosteroids. However, the precise clinical value of POF in the treatment of sarcoidosis and other lung diseases needs to be determined in further clinical trials.