Topical glucocorticoids inhibit neurogenic inflammation: involvement of lipocortin 1

Topical glucocorticoid treatment (betamethasone-17-valerate (0.018 mg/cm2, 3 h pretreatment) significantly inhibited neurogenic oedema formation induced by electrical antidromic stimulation (2 Hz, 15 V, 0.1 ms for 5 min) of the rat saphenous nerve; a response mediated by neuropeptides released from activated capsaicin-sensitive sensory C-fibres. Oedema formation was estimated by measurement of extravasation of i.v. injected 125I-albumin into skin. The inhibitory effect of the topical glucocorticoid was reversed by passive immunisation of rats with polyclonal antibody to the glucocorticoid-inducible anti-inflammatory protein lipocortin 1 (1 ml/kg, s.c., 24 h pretreatment) whilst a non-immune serum was without effect. Similarly the glucocorticoid receptor antagonist RU38486 (20 mg/kg, 2 and 20 h pretreatment) abrogated the response indicating specific binding to glucocorticoid receptors. Topical glucocorticoid treatment also inhibited the oedema produced by intradermal substance P (0.1 nmol) in the dorsal skin of rats. Topical glucocorticoid inhibited neurogenic oedema formation partly through a mechanism dependent upon lipocortin 1. This inhibition may be partly due to a post-junctional effect upon substance P activity/binding however a pre-junctional component cannot be excluded.