Interleukin 16 and T-cell chemoattractant activity in bronchoalveolar lavage 24 hours after allergen challenge in asthma

IL-16 has been shown to be one of the earliest CD4+ cell chemoattractants p resent in BAL 4-6 h after antigen challenge but little is known about its p ersistence and biological activity after 6 h. We determined the concentrati on of IL-16 using ELISA and the T-cell chemoattractant activity using a mod ified Boyden chamber assay in unconcentrated BAL fluid from 13 patients wit h mild asthma and 9 nonatopic control subjects at baseline and 24 h after s egmental allergen or saline challenge. Furthermore, the percentage of IL-16 -producing T cells was determined in the different samples of BAL fluid usi ng a flow cytometric intracellular cytokine assay. Although no substantial levels of IL-16 protein were detectable in BAL fluid from control subjects and patients with asthma at baseline and after saline challenge, IL-16 conc entrations were significantly elevated in patients with asthma after allerg en challenge (median, 97 pg/ml; range, 38-362 pg/ml; p < 0.01). Furthermore , there was an increased T-cell chemoattractant activity after allergen cha llenge in patients with asthma (p < 0.01), which could be blocked by preinc ubation with anti-IL-16 antibodies and which correlated significantly with the IL-16 protein levels (R = 0.90, p < 0.01) and with the level of Fas lig and expression on BAL CD4+ cells (R = 0.80, p < 0.05). A high percentage (m ean 70-90%) of CD4+ and CD8(+) cells stained positively for IL-16 in both p atients with asthma and control subjects without differences after allergen or saline challenge. These data demonstrate that the increased chemotactic activity for T cells in patients with asthma is mainly attributable to IL- 16. Although T cells by themselves are able to produce IL-16, other cells, such as epithelial cells, have to be considered as further sources for this cytokine in patients with asthma.