Effect of ingested pentoxifylline on the ex vivo neutrophil function of patients with varicose leg ulcers

Article type: Research Article

Authors: Crouch, S.P.M. | Saihan, E.M. | Fletcher, J.

Affiliations: Medical Research Centre, City Hospital, Nottingham, UK | Department of Dermatology, University Hospital, Queens Medical Centre, Nottingham, UK

Abstract: Polymorphonuclear leukocytes (PMN) appear to play a role in the pathogenesis of leg ulceration through tissue damage occurring as a result of these cells being trapped within the capillaries in anoxic tissue. The aim of this study was to determine whether ingestion of a 400mg slow release tablet of pentoxifylline (PTOX) would cause a reduction in the ex vivo responses of PMN isolated from patients with varicose leg ulcers. Superoxide anion production, as measured by lucigenin-enhanced chemiluminescence was significantly reduced at 2 and 4 hours post-ingestion in response to stimulation by formylmethionylleucylphenylalanine (FMLP) and C5a des arg in zymosan activated serum (ZAS). The response to FMLP was reduced by 39% (p=0.014) at 2 hours and by 32% (p=0.029) at 4 hours. The response to ZAS was reduced by 52% at 2 hours (p=0.007) and 50% at 4 hours (p=0.0104). Upregulation of the adhesion molecule CD11b in response to FMLP and ZAS was also significantly reduced in the patient group at 2 (p=0.010 for both stimuli) and 4 hours after ingestion (FMLP, p=0.0212; ZAS, p=0.0150), although the unstimulated expression of this molecule remained constant. There were no significant differences in the PMN responses observed when data for the patients was compared with the control group. These results suggest that the previous in vitro and ex vivo observations with PTOX on PMN from normal subjects can be reproduced with cells from patients suffering with varicose leg ulcers. PTOX may reduce recruitment and activation of further cells into the inflammatory foci and thus help prevent exacerbations of inflammation.

Keywords: pentoxifylline, polymorphonuclear leukocytes, varicose leg ulcers, superoxide anions, lactoferrin, adhesion molecules

DOI: 10.3233/CH-1994-14308

Journal: Clinical Hemorheology and Microcirculation, vol. 14, no. 3, pp. 379-392, 1994