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.


CONCLUSIONS
Our results may be the basis for clinical trials to evaluate the role of pentoxifylline as an immunotherapeutic agent in the treatment of EAA.
Department of Pneumology and Allergy, Ruhrlandklinik, Medical Faculty, University of Essen, Essen, Germany.
Zhaohui
Z
Tong
Baomin
B
Chen
Huaping
H
Dai
Peter C
PC
Bauer
Josune
J
Guzman
Ulrich
U
Costabel
D000328:Adult; D000368:Aged; D000542:Alveolitis, Extrinsic Allergic / Q000188:drug therapy* / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D003907:Dexamethasone / Q000276:immunology / Q000494:pharmacology; D005260:Female; D006401:Hematologic Agents / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000276:immunology / Q000494:pharmacology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006401:Hematologic Agents; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D003907:Dexamethasone; D010431:Pentoxifylline