Effect of methylprednisolone and polymyxin B sulfate on endotoxin-induced inhibition of human neutrophil chemotaxis.

Abstract

Abstract We have found that Escherichia coli endotoxin (1 ng/ml) inhibits neutrophil chemotaxis toward C5a by 85% but has no effect on chemotaxis toward two bacteria-derived chemotactic factors. We investigated the influence of methylprednisolone and polymyxin B on the inhibition of chemotaxis by endotoxin, since these two drugs are known to inhibit some of the biological effects of endotoxin. In the presence of methylprednisolone (5 × 10 −5 M), the IC 50 for endotoxin was increased from 0.3 to 2.2 ng/ml. Hydrocortisone at 4.5 × 10 −4 M and dexamethasone at 1.25 × 10 −5 M were as effective in inhibiting endotoxin as 5 × 10 −5 M methylprednisolone. Desoxycorticosterone, testosterone, and estradiol-17B had no such effect. In the presence of polymyxin B (2 μg/ml), the IC 50 for endotoxin was increased to 12 ng/ml. In the presence of both polymyxin B (2 μg/ml) and methylprednisolone 5 × 10 −5 M, the IC 50 for endotoxin was increased to 60 ng/ml. In separate experiments, methylprednisolone appeared to exert its effect by interacting with the neutrophil, whereas polymyxin B acted, at least in part, directly on the endotoxin molecule to block its chemotactic inhibitory activity. We conclude that the inhibition of human neutrophil chemotaxis by endotoxin can be antagonized by glucocorticoids and by polymyxin B. Methylprednisolone and polymyxin B appear to act at different sites, and in combination they have a supra-additive effect.