Endocrine disorders render rats hyporeactive to non-steroidal but not to steroidal anti-inflammatory drugs

The effect of cortisol (10 and 20 mg kg-1 day-1, sc), indomethacin (2 and 4 mg kg-1 day-1, po) and piroxicam (10 and 20 mg kg-1 day-1, po) on the proliferative component of inflammation was investigated in normal, diabetic, adrenalectomized and diabetic-adrenalectomized rats using the cotton pellet test. Whereas cortisol was equally effective in preventing granulation tissue formation in all groups of animals, indomethacin and piroxicam were much less active in animals with hormonal dysfunctions. Indomethacin and piroxicam reduced thymus weight of normal and diabetic animals as much as cortisol. This was taken to be a strong indication of the effect of these non-steroidal drugs on the adrenal cortex leading to increased secretion of adrenal corticosteroids. We conclude that at least part of the anti-inflammatory effect of indomethacin and piroxicam, in the present experiments, can be ascribed to the release of endogenous corticosteroids. This would explain the decreased sensitivity of adrenalectomized animals to the non-steroidal anti-inflammatory drugs used. An additional component, however, seems to be necessary for the full expression of the anti-inflammatory effect of these drugs, since diabetic animals were also less responsive to them. When both components were absent, as in diabetic-adrenalectomized animals, indomethacin and piroxicam were practically devoid of an anti-inflammatory effect.