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.
D000287:Administration, Topical; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D001623:Betamethasone / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D005938:Glucocorticoids / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D017305:Annexin A1; D005938:Glucocorticoids; D015735:Mifepristone; D001623:Betamethasone