Bradykinin is increased during acute and chronic inflammation: therapeutic implications.
Bradykinin is a potent pain-producing substance, yet little is known about its role in inflammation. The present study measured circulating levels of immunoreactive bradykinin in a clinical model of acute inflammation (oral surgery) and chronic inflammation (rheumatoid arthritis) and in the rat carrageenan model of inflammation. The effects of a kallikrein inhibitor (soybean trypsin inhibitor) on blocking bradykinin synthesis in vitro and its analgesic actions in the rat model were also evaluated. Levels of immunoreactive bradykinin increased threefold to fourfold during oral surgery. Levels were twofold to threefold greater in patients with rheumatoid arthritis compared with control subjects. Levels of immunoreactive bradykinin increased twofold in rats during carrageenan inflammation. Soybean trypsin inhibitor blocked synthesis of bradykinin in vitro and possessed analgesic activity in rats. The results indicate that the bradykinin system is activated during inflammation. Kallikrein inhibitors may represent a new class of analgesic/antiinflammatory drugs.
Hargreaves
K M
KM
Neurobiology and Anesthesiology Branch, National Institute of Dental Reserch, Bethesda, MD 20892.
Troullos
E S
ES
Dionne
R A
RA
Schmidt
E A
EA
Schafer
S C
SC
Joris
J L
JL
D000328:Adult; D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents; D001172:Arthritis, Rheumatoid / Q000097:blood; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002351:Carrageenan; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D013515:Surgery, Oral / Q000009:adverse effects; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D014361:Trypsin Inhibitors; D002351:Carrageenan; D001920:Bradykinin