Comparative study on effects of pentoxifylline, prednisolone and colchicine in experimental alveolitis.
Neutrophil alveolitis is a hallmark of cryptogenic fibrosing alveolitis (CFA), known for its poor prognosis. Corticosteroids, as the remedy of choice, are ineffective in a majority of patients. More and more evidence indicates that pentoxifylline (POF) could be an effective therapeutic alternative. Furthermore, colchicine has been proposed for therapy of CFA for many years now. We conducted an experimental study comparing the efficacy of these drugs in preventing neutrophil alveolitis in vivo. Alveolitis was induced in male rats by intratracheal instillation of bleomycin. Treatment consisted of daily injections of POF i.p., colchicine i.p., or prednisolone i.m. After 8 days the animals were sacrificed and body weights, cell differentials in BAL, amount of proliferating interstitial cells as determined by KI-67 staining of lung tissue, and collagen concentrations in lungs were determined. Bleomycin instillation was followed by a significant weight loss in the animals, a neutrophil alveolitis in BAL and an increased amount of proliferating cells in lung interstitium. POF significantly inhibited any of the parameters named, whereas prednisolone and colchicine had little effect. Data cannot be applied directly in human disease. There are however many similarities between CFA and bleomycin-induced lung injury and alveolitis. We conclude that POF is an effective inhibitor of neutrophil alveolitis, whereas neither colchicine nor prednisolone exerted significant influence in our model. We suggest POF effects should be further investigated regarding anti-inflammatory and anti-fibrotic properties.
Entzian
P
P
Department of Clinical Medicine, Research Center Borstel. pentzian@fz-borstel.de
Zähringer
U
U
Schlaak
M
M
Gerlach
C
C
Galle
J
J
Zabel
P
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003078:Colchicine / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000276:immunology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010431:Pentoxifylline / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; D010975:Platelet Aggregation Inhibitors; D003094:Collagen; D011239:Prednisolone; D010431:Pentoxifylline; D003078:Colchicine