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 lavage (BAL) cells induced hyperreactivity of the trachea in vitro. As both interleukin-5 (IL-5) and substance P (SP) appeared to be involved, the effect of these mediators was examined in vivo. Tracheae were incubated with BAL cells from ovalbumin or saline challenged animals, and from naive animals, in the absence or presence of either IL-5, SP, or both. 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 an increase (30 +/- 10%) in the maximal response to histamine. The hyperreactivity could be completely inhibited by co-incubation with 5-lipoxygenase inhibitor, AA861. The hyperreactivity could be mimicked by incubation of tracheae with BAL cells from naive animals in the presence 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 induced a significant increase in the number of eosinophils (67 +/- 22%) and eosinophil peroxidase (EPO) activity (94 +/- 33%) in BAL cells. The simultaneous administration of IL-5 and SP did not potentiate the hyperreactivity and eosinophilia observed with IL-5 alone. These data suggest that IL-5 is important in the recruitment of eosinophils, whereas both IL-5 and substance P are involved in the induction of airway hyperreactivity.

This article has been cited by other articles:

				S. Teramoto, H. Tanaka, S. Kaneko, and S. Abe Neurokinin-1 and Neurokinin-2 Antagonism Inhibits Long-term Acid Fog-Induced Airway Hyperresponsiveness Chest, February 1, 2003; 123(2): 524 - 529. [Abstract] [Full Text] [PDF]

				C. M. Evans, K. E. Belmonte, R. W. Costello, D. B. Jacoby, G. J. Gleich, and A. D. Fryer Substance P-induced airway hyperreactivity is mediated by neuronal M2 receptor dysfunction Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L477 - L486. [Abstract] [Full Text] [PDF]

				M. SCHUILING, A. B. ZUIDHOF, J. ZAAGSMA, and H. MEURS Involvement of Tachykinin NK1 Receptor in the Development of Allergen-induced Airway Hyperreactivity and Airway Inflammation in Conscious, Unrestrained Guinea Pigs Am. J. Respir. Crit. Care Med., February 1, 1999; 159(2): 423 - 430. [Abstract] [Full Text]

				A. D. KRANEVELD, F. P. NIJKAMP, and A. J. M. VAN OOSTERHOUT Role for Neurokinin-2 Receptor in Interleukin-5-induced Airway Hyperresponsiveness but not Eosinophilia in Guinea Pigs Am. J. Respir. Crit. Care Med., July 1, 1997; 156(2): 367 - 374. [Abstract] [Full Text]