Modulation of the acute phase response and in vitro measurement of interleukin-1 activity following administration of dexamethasone to adjuvant-arthritic rats.
Adjuvant-arthritic (AA) rats were medicated with dexamethasone to determine if this glucocorticoid suppressed the activity of interleukin-1 (IL-1) or the acute phase response. Dexamethasone (0.1 mg/kg, p.o.) administered daily for two weeks to AA rats, significantly (p less than or equal to 0.01) decreased high splenic IL-1 production (60% inhibition). Dexamethasone at a 0.5 mg/kg dose reduced AA rat splenic IL-1 production below normal (100% inhibition). In addition, dexamethasone significantly inhibited the AA rat acute phase response as measured by reduction of plasma C-reactive protein levels and enhancement of plasma albumin and iron levels. Following medication with 0.02, 0.1 or 0.5 mg/kg dexamethasone, high plasma C-reactive protein levels decreased by 33, 77 and 95% respectively, compared to untreated AA controls. Under the same dosing regimen of 0.02, 0.1 or 0.5 mg/kg dexamethasone, plasma albumin levels increased by 44, 128 and 239% respectively, while plasma iron levels rose by 19, 64 and 98% respectively, compared to AA controls. At the 0.02, 0.1 and 0.5 mg/kg doses dexamethasone also significantly reduced injected and noninjected paw swelling in AA rats. In view of the ability of dexamethasone to decrease IL-1 production and the acute phase response often associated with it, it is possible that part of the anti-inflammatory activity of dexamethasone may stem from inhibition of IL-1 formation in vivo.
Connolly
K M
KM
Department of Chemotherapy, Glaxo Inc., Research Triangle Park, NC 27709.
Stecher
V J
VJ
LaBrie
T
T
Fluno
C
C
D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D002097:C-Reactive Protein / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000032:analysis*; D007501:Iron / Q000097:blood; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D051381:Rats; D011917:Rats, Inbred Lew; D012709:Serum Albumin / Q000032:analysis
D007375:Interleukin-1; D012709:Serum Albumin; D003907:Dexamethasone; D002097:C-Reactive Protein; D007501:Iron; D010741:Phospholipases A