ROLE OF INTERLEUKIN-5 AND SUBSTANCE-P IN DEVELOPMENT OF AIRWAY HYPERREACTIVITY TO HISTAMINE IN GUINEA-PIGS

In this study, we examined the mechanism by which bronchoalveolar lava ge (BAL) cells induced hyperreactivity of the trachea in vitro. As bot h interleukin-5 (IL-5) and substance P (SP) appeared to be involved, t he effect of these mediators was examined in vivo. Tracheae were incub ated with BAL cells from ovalbumin or saline challenged animals, and f rom naive animals, in the absence or presence of either IL-5, SP, or b oth, In addition, the effect of intra-airway application of IL-5, SP, both, or vehicle on tracheal hyperreactivity was examined. Incubation of tracheae with BAL cells from ovalbumin challenged animals induced a n increase (30+/-10%) in the maximal response to histamine, The hyperr eactivity could be completely inhibited by co-incubation with the 5-li poxygenase Inhibitor, AA861. The hyperreactivity could be mimicked by incubation of tracheae with BAL cells from naive animals in the presen ce of IL-5 and SP. After in vivo administration of either IL-5 or SP, maximal responses to histamine were increased and amounted to 105+/-35 and 101+/-37%, respectively, Administration of IL-5 but not SP induce d a significant increase in the number of eosinophils (67+/-22%) and e osinophil peroxidase (EPO) activity (94+/-33%) in BAL cells, The simul taneous administration of n-5 and SP did not potentiate the hyperreact ivity and eosinophilia observed with IL-5 alone. These data suggest th at IL-5 is important in the recruitment of eosinophils, whereas both I L-5 and substance P are involved in the induction of airway hyperreact ivity. (C)ERS Journals Ltd 1996.