Glucocorticoids suppress levels of immunoreactive bradykinin in inflamed tissue as evaluated by microdialysis probes.
Although circulating bradykinin increases during surgery, concentrations remain unknown in the biologically relevant compartment, the inflamed tissue. We have developed a new method, using microdialysis probes, for collecting tissue samples of immunoreactive bradykinin in both postoperative patients and rats injected with carrageenan. In vitro studies determined optimal flow rate, that dialysate levels of immunoreactive bradykinin were linearly related to external concentrations, and that the probes do not activate bradykinin synthesis. In oral surgery patients, tissue levels of immunoreactive bradykinin peaked approximately 3 hours after surgery. Preoperative administration of methylprednisolone (125 mg) reduced immunoreactive bradykinin levels by 62% (p less than 0.001) compared with placebo. Comparison of bradykinin levels to concurrent pain revealed a counterclockwise hysteresis, suggesting a delay between peak levels of bradykinin in the effect compartment and pain. In rats, dexamethasone suppressed tissue levels of immunoreactive bradykinin. The glucocorticoid suppression was dependent on de novo protein synthesis. Microdialysis appears to be a novel and useful method for measuring the peripheral release of bradykinin and, possibly, other inflammatory mediators.
Hargreaves
K M
KM
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Md.
Costello
A
A
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001920:Bradykinin / Q000032:analysis / Q000378:metabolism*; D002351:Carrageenan; D003956:Dialysis / Q000295:instrumentation / Q000379:methods*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D010149:Postoperative Pain / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005938:Glucocorticoids; D015735:Mifepristone; D000841:Anisomycin; D002351:Carrageenan; D001920:Bradykinin; D008775:Methylprednisolone