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Angiostatic cortexone‐heparin combination treatment suppresses chronic granulomatous inflammation in mice
Author(s) -
Dunn Colin J.,
Galinet Louise A.
Publication year - 1991
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430230407
Subject(s) - heparin , angiogenesis , inflammation , medicine , granuloma , subcutaneous injection , infiltration (hvac) , immunology , endocrinology , pharmacology , physics , thermodynamics
Combined steroid‐heparin therapy has been shown to inhibit angiogenesis and tumor growth. We therefore decided to test the antiinflammatory activity of this combination therapy using “cotton pellet” and “delayed‐type hypersensitivity” granuloma reactions, which display a high degree of angiogenesis. Subcutaneous injection of cortexone (deoxycorticosterone) caused significant suppression of both granulomatous reactions only when administered to mice receiving heparin ad libitum in the drinking water. Significant reduction in inflammatory leukocyte infiltration and angiogenesis was also observed histologically compared with controls. Coretexone or heparin alone failed to alter the granulomatous responses. Hematomas were observed only in the cortexone‐heparin combination therapy group at the cortexone subcutaneous injection site suggesting a possible effect on endothelial cell integrity; blood coagulation times remained unaltered, and no evidence of hemorrhage was observed at autopsy. Modest loss in thymic weight occurred only in mice receiving cortexone (100 mg/kg/day s.c.), regardless of concomittant heparin treatment. We conclude that combination cortexone‐heparin treatment causes significant inhibition of chronic granulomatous inflammation, which is independent of glucocorticoid or coagulation mechanisms. Further investigation is required to determine whether this effect is accomplished via inhibition of macrophage function, endothelial cell proliferation, or interference with tissue matrix metabolism.