Effects of bacterial endotoxin and corticosteroids on plasma concentrations of alpha 2 macroglobulin, haptoglobin and fibrinogen in rats.

Bacterial endotoxin injected into rats resulted in increased plasma concentration of alpha 2 macroglobulin, haptoglobin and fibrinogen. Cortisone acetate injected i.m. by itself was sufficient to increase the plasma concentration of haptoglobin by 54% and to a lesser extent the concentrations of the other two proteins. When cortisone acetate and/or cortisol succinate were injected simultaneously with varying doses of endotoxin, the effects of the corticosteroid differed for each plasma protein. Doubtless because of the effect of cortisone by itself the slope of the dose-response relationship for haptoglobin was greatly reduced. In contrast to this the slope for alpha 2 macroglobulin was reduced and that for fibrinogen was unaffected. These findings suggest that, if effects due to endogenous corticosteroids are to be avoided, increases in plasma fibrinogen will serve best as indicators of stimulation of the acute-phase response. Since, however, the relative increase of alpha 2 macroglobulin due to the lowest dose of endotoxin was much greater than that of fibrinogen, increases in concentration of the former protein represent the most sensitive indication of the acute-phase response. Consideration of the responses in individual rats has made possible division into those with more or less than average increases for all 3 plasma proteins and those showing irregular responses. Especially in the group which had received the lowest dose of endotoxin, a much larger number than would be expected on a random basis was found to respond regularly with either more or less than average increases for all 3 proteins.