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

Abstract

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.

Histamine H4 and H2 Receptors Control Histamine-Induced Interleukin-16 Release from Human CD8+ T Cells

“…Histamine has been discussed as a mediator of asthma for a long time (reviewed in Barnes et al, 1998) and one of the mediators induced by this biogenic amine is IL-16. Indeed, this CD4 ϩ cell chemoattractant was found in lungs of asthma patients following challenge Laberge et al, 1995;Krug et al, 2000), and intervention strategies against IL-16 have been successful in experimental animal models mimicking asthma symptoms (Hessel et al, 1998;de Bie et al, 1999). However, cimetidine treatment of mice failed to significantly reduce IL-16 levels in the bronchoalveolar lavage fluid of Ag-challenged mice .…”

“…IL-16 is further produced by many other cell types, including mast cells, eosinophils, B cells, dendritic cells, and epithelial cells (reviewed in Cruikshank et al, 2000). IL-16 has been found in the bronchoalveolar fluid of allergen-or histamine-challenged asthmatics Mashikian et al, 1998;Krug et al, 2000) and is increasingly expressed in the bronchial mucosa of atopic asthmatics (Laberge et al, 1997) by eosinophils and mast cells (Laberge et al, 1999). Through binding to its receptor (CD4), IL-16 is believed to play an important role in the recruitment of CD4 ϩ T cells into the lungs of asthmatic patients.…”

IL-16 Promotes Leukotriene C4 and IL-4 Release from Human Eosinophils via CD4- and Autocrine CCR3-Chemokine-Mediated Signaling

“…In forms of allergic inflammation, including asthma, IL-16 has been found to be prominent. IL-16 was increased in the bronchial mucosa and sputum of patients with atopic asthma (5,6) and in the bronchial mucosa and bronchoalveolar lavage fluids after segmental allergen challenge (7,8). Likewise, IL-16 increases in the nasal mucosa of patients with allergic rhinitis after experimental or seasonal allergen exposures (9,10).…”

Integrative Omics Approach Identifies Interleukin-16 as a Biomarker of Emphysema

“…IL-16 has also been associated with asthma in genetic studies (Burkart et al, 2006). In addition, bronchoalveolar lavage fluid (BALF) IL-16 increases in patients with asthma after exposure to an allergen (Krug et al, 2000). Two small studies of chronic bronchitis and COPD suggest a possible relationship between IL-16 and COPD.…”