Am. J. Respir. Crit. Care Med., Volume 162, Number 1, July 2000, 105-111

Interleukin 16 and T-cell Chemoattractant Activity in Bronchoalveolar Lavage 24 Hours after Allergen Challenge in Asthma

NORBERT KRUG, WILLIAM W. CRUIKSHANK, THOMAS TSCHERNIG, VEIT J. ERPENBECK, KERSTIN BALKE, JENS M. HOHLFELD, DAVID M. CENTER, and HELMUT FABEL

Departments of Respiratory Medicine and Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany; and Pulmonary Center Boston, University School of Medicine, Boston, Massachusetts

IL-16 has been shown to be one of the earliest CD4⁺ cell chemoattractants present in BAL 4-6 h after antigen challenge but little is known about its persistence and biological activity after 6 h. We determined the concentration of IL-16 using ELISA and the T-cell chemoattractant activity using a modified Boyden chamber assay in unconcentrated BAL fluid from 13 patients with mild asthma and 9 nonatopic control subjects at baseline and 24 h after segmental allergen or saline challenge. Furthermore, the percentage of IL-16-producing T cells was determined in the different samples of BAL fluid using 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 concentrations were significantly elevated in patients with asthma after allergen challenge (median, 97 pg/ml; range, 38-362 pg/ml; p < 0.01). Furthermore, there was an increased T-cell chemoattractant activity after allergen challenge in patients with asthma (p < 0.01), which could be blocked by preincubation 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 ligand expression on BAL CD4⁺ cells (R = 0.80, p < 0.05). A high percentage (mean 70-90%) of CD4⁺ and CD8⁺ cells stained positively for IL-16 in both patients 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.

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