Extrinsic allergic alveolitis: inhibitory effects of pentoxifylline on cytokine production by alveolar macrophages
Received 23 May 2003; accepted 30 August 2003.
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) α, interleukin (IL) 1β, 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-α 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-α. Pentoxifylline and dexamethasone also inhibited the LPS-stimulated production of all cytokines except IL-1β 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.
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*Department of Pneumology and Allergy, Ruhrlandklinik, Medical Faculty, University of Essen, Essen, Germany.
†General and Experimental Pathology, Ruhr University, Bochum, Germany.
Requests for reprints should be addressed to: Ulrich Costabel, MD, Ruhrlandklinik, Tüschener Weg 40, 45239 Essen, Germany
ABSTRACT