A role for endogenous histamine in interleukin-8-induced neutrophil infiltration into mouse air-pouch: investigation of the modulatory action of systemic and local dexamethasone

摘要: 1. When injected into a 6-day-old mouse air-pouch, human recombinant interleukin-8 (IL-8; 0.03-3 micrograms) induced, in dose-dependent fashion, an accumulation of neutrophils which could be reliably assessed 4 h after the injection. No protein extravasation was measured above values obtained with vehicle alone (carboxymethylcellulose, CMC, 0.5% w/v phosphate-buffered solution, PBS). 2. The IL-8 effect (routinely evaluated at 1 microgram dose) inhibited neither by local administration actinomycin D (1 microgram) nor systemic treatment indomethacin mg kg-1, i.v.), BWA4C (5 p.o.), methysergide (6 i.p.) and RP67580 (2 i.p.). 3. Treatment mice H1 antagonist, mepyramine (1-10 resulted inhibition cell elicited chemokine, maximal reduction approximately 50-60%. not due to non specific neutrophil function, since this drug did modify infiltration response challenge interleukin-1 beta (20 ng) or CMC any extent. Moreover, counts peripheral blood film respect controls. Two other antagonists, chemically unrelated mepyramine, diphenhydramine (9 triprolidine (0.5 i.p.), IL-8-induced migration similar extent (approximately 50-60%), whereas H2 ranitidine without effect. 4. concept that endogenous histamine involved strengthened two ways: (i) addition (0.2-2 microg) small dose (0.3 potentiated elicitation induced chemokine having on its own; (ii) greatly impaired animals depleted mast amines sub-chronic day) compound 48/80 according established protocol.5. glucocorticoid dexamethasone (Dex; 1-50 microg per mouse, i.v., corresponding 0.03-1.5 given i.v. 2 prior IL-8) potently approximate ED50 5 (~ 0.3 kg-1 , i.v.). Passive immunisation polyclonal sheep serum raised against steroid-inducible anti-inflammatory lipocortin (LCl)abolished inhibitory action Dex control effect.6. Local ineffective when systemically also reduced IL-8, either combination histamine. This (~50%), seen hydrocortisone (30 microg), prevented concomitant steroid antagonist RU38486 (10 indicating involvement receptor response.7. These findings characterize further mechanisms underlying PMN recruitment vivo, point role for glucocorticoids, as some models, appears LCl-dependent these drugs are LCl independent steroids locally.