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.
Tong
Zhaohui
Z
Department of Pneumology and Allergy, Ruhrlandklinik, Medical Faculty, University of Essen, Essen, Germany.
Chen
Baomin
B
Dai
Huaping
H
Bauer
Peter C
PC
Guzman
Josune
J
Costabel
Ulrich
U
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