Hammerschmidt D E, Knabe A C, Silberstein P T, Lamche H R, Coppo P A
Department of Medicine, University Hospital, Minneapolis, Minnesota 55455.
Inflammation. 1988 Jun;12(3):277-84. doi: 10.1007/BF00920079.
Noting that corticosteroid doses required for protection in shock models exceeded those required to saturate glucocorticoid receptors in mammalian cells, we postulated a nonspecific physicochemical effect of steroids upon the cell membrane, and therefore tested three noncorticoid steroids for their effects on granulocyte function. All three (conjugated equine estrogen, a synthetic progestogen, and a synthetic androgen) behaved in manner analogous to corticoids at similar concentrations, inhibiting granulocyte aggregation, chemotaxis, and chemiluminescence, as well as binding to the granulocytes of the synthetic oligopeptide agonist f-Met-Leu-Phe. Estrogen was further shown to reduce granulocyte membrane fluidity, assessed by electron paramagnetic resonance. We propose that the unique effects of extremely high-dose corticosteroids are not mediated via the glucocorticoid receptor, but result rather from physicochemical effects of the drugs upon the membranes of effector cells.
