Involvement of kinins, mast cells and sensory neurons in the plasma exudation and paw oedema induced by staphylococcal enterotoxin B in the mouse

Intraplantar injection of staphylococcal enterotoxin B induces long-lasting oedema mediated by both cyclooxygenase and lipoxygenase products as well a s by neuropeptides from sensory nerves. This study was undertaken to furthe r clarify the role of peripheral primary afferent sensory nerves in staphyl ococcal enterotoxin B (25 mu g/paw)-induced plasma extravasation and oedema formation. The tachykinin NK2 receptor antagonist (S)-1-[2-[3-(3,4-dichlor ophenyl)-1 (3-isopropoxyphenylacetyl)piperidin-3-y] ethyl]4-phenyl-1 azonia bicyclo [2.2.2]octane cloride (SR140333; 120 nmol/kg, s.c. + 120 nmol/kg, i .v.) significantly inhibited plasma exudation and paw oedema evoked by stap hylococcal enterotoxin B. The tachykinin NK, receptor antagonist (S)-N-meth yl-N[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl] (SR 48968) had no effect on the staphylococcal enterotoxin B-induced responses. The bradykinin B-2 receptor antagonist D-Arg-[Hyp(3),Thi(5),D-TiC7,OiC(8)] bradykinin (Hoe 140; 400 nmol/kg, i.v.) significantly reduced staphylococca l enterotoxin B-induced responses. The magnitude of the inhibition observed with Hoe 140 alone was similar to that caused by concomitant treatment of animals with SR140333 and Hoe 140, suggesting that there is a final common pathway. Additionally, SR140333 given alone reduced bradykinin (3 nmol/paw) -induced paw oedema. The vanilloid receptor antagonist N-[2-(4-chlorophenyl ) ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamide (capsazepine; 100 mu mol/kg) significantly reduced staphylococcal enteroto xin B-induced responses. The 5-HT receptor antagonist methysergide (10 mg/k g, i.v.) and the histamine H-1 receptor antagonist mepyramine (10 mg/kg, i. v.) produced a significant reduction in paw oedema whereas plasma exudation was reduced only by methysergide. In diabetic mice, exudation and oedema e voked by staphylococcal enterotoxin B were markedly reduced. Acute administ ration of insulin (20 UI/kg, s.c., 30 min before) did not restore the incre ased permeability induced by staphylococcal enterotoxin B. We conclude that plasma exudation and paw oedema in response to staphylococcal enterotoxin B are a consequence of a complex neurogenic response involving direct activ ation of vanilloid receptors on sensory nerves, release of kinins and subse quent activation of bradykinin B-2 receptors at a prejunctional level, and direct or indirect degranulation of mast cells. (C) 2000 Elsevier Science B .V. All rights reserved.