EARLY IDENTIFICATION OF INTERLEUKIN-16 (LYMPHOCYTE CHEMOATTRACTANT FACTOR) AND MACROPHAGE INFLAMMATORY PROTEIN 1-ALPHA (MIP1-ALPHA) IN BRONCHOALVEOLAR LAVAGE FLUID OF ANTIGEN-CHALLENGED ASTHMATICS

Accumulation of CD4(+) interleukin (IL)-2R(+) lymphocytes in the airways of asthmatics is generally attributed to the presence of chemoattractant cytokines. The precise mechanism for the initiation of the earliest CD4(+) lymphocyte infiltration and activation is unknown. In this study, we describe for the first time the presence of lymphocyte chemoattractant activity in the bronchoalveolar lavage (BAL) fluid obtained from asthmatics 6 h after antigen challenge. The majority of the chemoattractant activity at this early time point is represented by IL-16 (lymphocyte chemoattractant factor), a CD4(+) cell-specific chemoattractant and growth factor. In addition to IL-16, macrophage inflammatory protein la (MIP1 alpha) chemotactic bioactivity was detected in significant levels. While IL-16, MIP1 alpha, and IL-8 were all identified by enzyme-linked immunosorbent assay, the great majority of the lymphocyte chemoattractant activity in the BAL fluid after antigen challenge is attributable to IL-16 and MIP1 alpha. There were no detectable levels of IL-16 nor MIP1 alpha in BAL fluid of antigen-challenged normal subjects nor atopic nonasthmatics nor in saline-challenged lobes from the asthmatics. The identification of multiple lymphocyte chemoattractants early after antigen challenge suggests a complex cellular, as well as chemoattractant cytokine, profile in initiating the CD4(+) T cell-mediated inflammatory process that is specific for the atopic asthmatic phenotype.