PRETREATMENT WITH AN ANTIBODY TO INTERLEUKIN-5 PREVENTS LOSS OF PULMONARY M(2) MUSCARINIC RECEPTOR FUNCTION IN ANTIGEN-CHALLENGED GUINEA-PIGS

Inhalational challenge with antigen decreases the function of inhibito ry M(2) muscarinic autoreceptors on parasympathetic nerves in the lung , increasing the release of acetylcholine from the vagus nerves and po tentiating vagally induced bronchoconstriction. It is possible that eo sinophils cause M(2) receptor dysfunction, perhaps by releasing positi vely charged proteins that are M(2) receptor antagonists. Because of t he probable role of interleukin-5 in initiating and maintaining the eo sinophil infiltration, we tested the function of neuronal M(2) recepto rs in antigen-challenged guinea pigs after pretreatment with a monoclo nal antibody to interleukin-5 (TRFK-5). Ovalbumin was given intraperit oneally to sensitize the animals. Three weeks later, the animals were injected intraperitoneally with either TRFK-5 (240 mu g/kg i.p.) or sa line. Beginning three days later, they were challenged with an ovalbum in aerosol for 5 min on each of four consecutive days. M(2) receptor f unction was tested 24 h after the last antigen challenge, Electrical s timulation of both vagi caused bronchoconstriction and bradycardia. In control animals, pilocarpine attenuated, and gallamine potentiated, v agally induced bronchoconstriction by stimulating and blocking neurona l M(2) muscarinic receptors, respectively, In challenged animals that did not receive TRFK-5, these effects were markedly reduced, confirmin g M(2) receptor dysfunction. In TRFK-5-treated guinea pigs, the effect s of both pilocarpine and gallamine were the same as those in control animals, demonstrating normal M(2) receptor function. Pretreatment wit h TRFK-5 selectively inhibited the migration of eosinophils into the l ungs as measured by lung lavage. Thus the function of M(2) muscarinic receptors in antigen-challenged guinea pigs can be protected by inhibi ting eosinophil influx into the lungs.