Modulation of alpha 2-acute phase globulin serum concentration in turpentine- and immune complex-challenged rats by dexamethasone and adrenaline: evidence for a synergistic mode of action.
The acute phase response (APR) induced by immune complexes or turpentine and modulated by dexamethasone as well as adrenaline was investigated in intact, sham-adrenalectomized and adrenalectomized rats. The serum level of alpha 2-acute phase globulin was examined by means of electroimmunodiffusion, and the complex serum protein profile was studied using the crossed-IE. Dexamethasone administration increased the alpha 2-acute phase globulin concentration weakly over a wide dose range whereas rats dosed with adrenaline responded strongly over a small dose range. Turpentine but not immune complex challenge provoked an almost complete acute phase protein profile as well as a moderate alpha 2-acute phase globulin elevation in adrenalectomized rats. After combined administration of the prophlogistic agents and dexamethasone or adrenaline a remarkably high alpha 2-acute phase globulin level was found (up to 14 mg/ml with about 0.05 mg/ml as base level). From these results a synergistic mode of action can be suggested. With crossed-IE some of the proteins could by divided in proteins responding in a glucocorticoid-dependent (e.g. alpha 2-acute phase globulin, haptoglobin) and -independent fashion (alpha 1-acute phase globulin), respectively. It can be concluded that glucocorticoids, catecholamines as well as cytokines are the main candidates for triggering the acute phase response; however, additional factors may also be of importance.
D000315:Adrenalectomy; D000818:Animals; D000936:Antigen-Antibody Complex / Q000008:administration & dosage*; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D014425:Turpentine / Q000633:toxicity*; D000511:alpha-Macroglobulins / Q000276:immunology / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D000511:alpha-Macroglobulins; D003907:Dexamethasone; D014425:Turpentine; D004837:Epinephrine