Increased airway resistance in asthma may be partly due to poor function of pulmonary surfactant. This study investigated the inflammatory changes of bronchoalveolar lavage fluid (BALF) and the performance of BALF surfactant in healthy control subjects (n = 9) and patients with mild allergic asthma (n = 15) before and after segmental challenge. BALF was obtained for baseline values, and 24 h after challenge with saline solution in one lung segment and with allergen in another. Cell counts, phospholipid and protein concentrations, and ratios of small to large surfactant aggregates (SA/LA) were analyzed. Surface tension was determined with a pulsating bubble surfactometer, and the ability of the BALF surfactant to maintain airway patency was assessed with a capillary surfactometer. Baseline values of control subjects and asthmatics were not different. Challenge with saline and antigen raised total inflammatory cells in both control subjects and asthmatics. Allergen challenge of asthmatics, but not of healthy volunteers, significantly increased eosinophils, proteins, SA/ LA, and surface tension at minimum bubble size, and diminished the time the capillary tube is open. In conclusion, allergen challenge in asthmatics induced surfactant dysfunction, probably mainly because of inhibiting proteins. During an asthma attack, narrow conducting airways may become blocked, which might contribute to an increased airway resistance.

T cell-derived cytokines play an important role in the pathogenesis of allergic asthma, but little is known about the cytokine profile of their different subsets. The aim of the present study was to investigate the cytokine production potential of CD4(+), CD8(+), or gammadelta(+) T cells derived from the bronchoalveolar space of mild atopic asthmatic subjects (n = 11) and nonatopic control subjects (n = 9) before and 24 h after segmental allergen challenge. The cytokine production was determined using the technique of intracellular cytokine detection by flow cytometry. Comparing asthmatic with control subjects we found no difference in the percentage of CD4(+), CD8(+), or gammadelta T cells in the bronchoalveolar lavage fluid before and after allergen challenge. Before allergen challenge the proportion of cells producing the cytokines interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-13 was not different in CD4(+) and CD8(+) cells. The major difference between the groups was an increased percentage of positive-staining cells for the T helper-(Th)2-cytokines IL-5 and IL-13 in the gammadelta T-cell subset. After allergen challenge, all T-cell subsets revealed a decreased proportion of cells producing the Th1-type cytokines IFN-gamma and IL-2. The percentage of IL-4- and IL-5-positive cells did not change in all subsets, and there was a decreased proportion of IL-13- positive cells in the CD4(+) subset. These findings indicate an increased Th2-cytokine profile in gammadelta T cells. After allergen challenge, the dysbalance between Th1 and Th2 cytokines was further accentuated by a reduction in Th1 cytokine-producing T cells.

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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