The monocyte-derived chemokine is released in the bronchoalveolar lavage fluid of steady-state asthmatics.

Infiltration of the airways by T helper type 2 (Th2) lymphocytes is a well-recognized feature of bronchial asthma. Monocyte-derived chemokine (MDC) is a potent attractant which activates Th2 lymphocytes via the chemokine receptor CCR4. We have investigated both leukocyte recruitment and MDC release into the airways of asthmatic patients. Differential cell counts in bronchoalveolar lavage (BAL) fluid showed that numbers of lymphocytes and eosinophils were elevated in asthmatics compared with normal subjects (median, 6.1 vs. 1.0 x 10(3)/ml, P < 0.005 and 1.4 vs. 0.24 x 10(3)/ml, P = 0.001, respectively). By enzyme-linked immunosorbent assay it was demonstrated that MDC concentrations were significantly elevated in BAL fluid from asthmatics compared with normals (medians 282 pg/ml, range 190-780 pg/ml vs. median 29 pg/ml range 17-82 pg/ml, P < 0.001). Interestingly, there was a significant correlation between MDC levels and the bronchoconstrictive response to methacholine [PC20 forced expiratory volume (FEV)1, r = -0.78, P = 0.001], suggesting that MDC may be involved in the severity of the disease. By immunohistochemistry, MDC was localized predominantly to the bronchial epithelium in bronchial biopsies derived from stable asthmatics. Moreover, primary human airway epithelial cells were found to release MDC upon cytokine stimulation. These findings suggest that MDC may play a major role in the pathogenesis of bronchial asthma.

Interleukin (IL)-4 and to a lesser extent either IL-13 or interferon-gamma regulate the production of eotaxin-2/CCL24 in nasal polyps.

BACKGROUND: Eotaxin-2/CCL24 is a potent eosinophil attractant that has been implicated in the recruitment of eosinophils in allergic disease. We have investigated whether the cytokines interleukin (IL)-4, IL-13, and interferon (IFN)-gamma regulate eotaxin-2/CCL24 in nasal polyps. METHODS: Nasal polyps were cultured in the presence of the cytokines described above and the concentration of eotaxin-2/CCL24 was measured in the culture supernatant. RESULTS: IL-4 was found to be the major stimulus for eotaxin-2/CCL24 production from nasal polyps followed by IL-13 and IFN-gamma. IL-4 induced eotaxin-2/CCL24 in a dose-dependent manner with concentrations as low as 0.1 ng/ml being able to induce eotaxin-2/CCL24. By immunohistochemistry, eotaxin-2/CCL24 immunoreactivity was localized to mononuclear cells in the IL-4 stimulated nasal polyp tissue. Interestingly, nasal turbinates obtained from patients suffering from nonallergic rhinitis (vasomotor rhinitis) were also found to release eotaxin-2/CCL24 both spontaneously and following cytokine stimulation with IL-4 and IFN-gamma being major inducers of this cytokine. CONCLUSIONS: All together these findings suggest that Th1 and Th2 cytokines may regulate eotaxin-2/CCL24 production in nasal polyps and nonallergic rhinits.