Abstract
Pretreatment of human monocytes with benoxaprofen for at least 2 h produced a dose-dependent abrogation of their adhesion to monolayers of cultured porcine endothelium with 0.05 μg/ml and 50.0 μg/ml of the drug inducing a mean 33% and 83% inhibition of adhesion respectively. When the endothelium was treated with the drug there was no modification of monocyte adhesion. In contrast, pretreatment of endothelium with 5.0 and 50.0 μg/ml benoxaprofen for at least 6 h, resulted in a mean 35% and 31% inhibition of polymorphonuclear cell (PMN) adhesion in 6/11 experiments. This inhibitory effect was not seen when drug-treated PMNs were added to endothelium. An impairment of monocyte chemotactic migration was only apparent with high concentrations of the drug (50 μg/ml). These results suggest that an important anti-inflammatory property of benoxaprofen is the inhibition of monocyte adhesion to vascular endothelium.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
W. Dawson, J.R. Boot, J. Harvey and J.R. Walker,The pharmacology of benoxaprofen with particular reference to effects on lipoxygenase product formation. Eur. J. Rheumatol. Inflammation5, 61–68 (1982).
D.J. Masters and R.M., McMillan,5-lipoxygenase from leucocytes. Brit. J. Pharmacol81, 70 (1984).
J.A. Salmon, G. Higgs, L. Tilling, S. Moncada and J.R. Vane,Mode of action of benoxaprofen, Lanceti, 848 (1984).
S.C.R. Meacock and E.A. Kitchen,Effects of the non-steroidal anti-inflammatory drug benoxaprofen on leucocyte migration. J. Pharm. Pharmacol.31, 366–370 (1979).
R. Dreher, B. Robe-Oltmanns, K. Firk and H. Seidel,Pathogenesis and therapy of rheumatoid inflammation. Immun. Infekt.14, 100–108 (1986).
E.J. Goetzl and F.H. Valone,Selective immobilization of human mononuclear phagocytes by benoxaprofen. Arthritis Rheum.25, 1486–1498 (1982).
G. Janossy, G.S. Panayi, O. Duke, M. Bofill, L.W. Poulter and G. Goldstein,Rheumatoid arthritis: a disease of T lymphocyte/macrophage immunoregulation. Lancetii, 839–844 (1981).
W.G. Spector, M.N. Walters and D.A. Willoughby,The origin of the mononuclear cells in inflammatory exudates induced by fibrinogen. J. Pathol. Bacteriol.90, 181–192 (1965).
K.A. Brown, J. Ferrie, B. Wilbourn and D.C. Dumonde,Benoxaprofen, a potent inhibitor of monocyte-endothelial cell interaction. Lancetii, 643 (1984).
D. De Bono,Effects of cytotoxic sera on endothelium in vitro. Nature252, 88–84 (1974).
S.D. Nathanson, P. Zamfirescu, S.I. Drew and S. Wilbur,Two-step separation of human peripheral blood monocytes on discontinuous density gradients of coloidal silicapolyvinylpyrrolidinone. J. Immunol. Methods18, 225–234 (1977).
J.P. Neoptolemos, H. Darby, E. Bolton and P.R.L. Bell,Monocyte chemotaxis: a simple measurement technique. Med. Lab. Sci.40, 291–294 (1983).
A.S. Ridolfo, R.H. Carmichael, K.A. DeSahte, R.F. Bergstrom, F. Rockhold, J.F. Nash and S.E. Fineberg,Clinical pharmacology of benoxaprofen. Eur. J. Rheumatol.5, 98–112 (1982).
R.A. Turner, L.S. Elliot, J.A. Johnson, E.L. McCrickard, W.J. Treadway and J.S. Kaufman,Effects of benoxaprofen on human neutrophil function. J. Rheumatol.11, 265–271 (1984).
W.J. Wallis, P.G. Beatty, H.O. Ochs and J.M. Harlan,Human monocyte adherence to cultured vascular endothelium: monoclonal antibody-defined mechanisms. J. Immunol.135, 2323–2330 (1985).
L.A. Boxer, J.M. Allen, M. Schmidt, M. Yoder and R.L. Baehner,Inhibition of polymorphonuclear leukocyte adherence by prostacyclin. J. Lab. Clin. Med.95, 672–678 (1980).
J.D. Pearson and J.L. Gordon,Granulocyte interactions with endothelium. InCellular Interactions, vol 107. (Eds J.T. Dingle and J.L. Gordon). Elsevier North Holland, vol 107. 1981.
M.R. Buchanan, M.J. Vazquez and M.A. Gimbrone Jr.,Arachidonic acid metabolism and the adhesion of human polymorphonuclear leukocytes to cultured vascular endothelial cells. Blood62, 8189–895 (1983).
S.C.R. Meacock, G.W. Civil, W. Dawson and E.A. Kitchen,The pharmacology of benoxaprofen with particular reference to effects on lipoxygenase product formation. Eur. J. Rheumatol. Inflammation5, 61–68 (1982).
R. Anderson, P.T. Lukey, S.P.E. Naudi and G. Joone,Benoxaprofen: a pro-oxidant anti-inflammatory drug? Agents and Actions14, 238–246 (1984).
K. Kragbolte, S. Ternowitz and T. Herlin,Normalization of monocyte chemotaxis precedes clinical resolution of psoriasis treated with benoxaprofen. Acta Derm. Venereal (Stockh)65, 319–323 (1985).
K.M. Simmons, K.A. Brown, A.P. Kirk, J.D. Perry and D.C. Dumonde,Enhanced chemotaxis of monocytes in rheumatoid arthritis. Brit. J. Rheumatol.26, 245–250 (1987).
K.A. Brown, T. Fernandes, A.P. Kirk and D.C. Dumonde,Enhanced adherence of rheumatoid monocytes to cultured endothelium. Brit. J. Rheumatol.25, (suppl) Abs 63 (1986).
B.R. Allen and S.M. Littlewood,Benoxaprofen: effect on cutaneous lesions in psoriasis. Brit. Med. J.285, 1241 (1982).
K. Kragbolte and T. Merlin,Benoxaprofen improves psoriasis: a double-blind study. Arch. Dermatol.119, 548 (1982).
M.W. Greaves,Pharmacology and significance of nonsteroidal drugs in the treatment of skin diseases. J. Am. Acad. Dermatol.16, 751–764 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brown, K.A., Ferrie, J., Wilbourn, B. et al. Benoxaprofen inhibits the adhesion of human monocytes to cultured vascular endothelium. Agents and Actions 28, 115–120 (1989). https://doi.org/10.1007/BF02022991
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02022991