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Increased Expression of the Chemoattractant Cytokines Eotaxin, Monocyte Chemotactic Protein-4, and Interleukin-16 in Induced Sputum in Asthmatic Patients^*

^* From the Meakins-Christie Laboratories (Dr. Taha) and Montreal Chest Research Institute (Drs. Laberge, Hamid, and Olivenstein), McGill University, and Ste-Justine Hospital, University of Montreal, Montreal, Quebec, Canada.

Correspondence to: Ronald Olivenstein, MD, Montreal Chest Institute, McGill University, 3650 St. Urbain St, Montreal, Quebec, Canada H2X 2P4; e-mail: rolive3{at}po-box.mcgill.ca

Background: Induced sputum from asthmatic patients has been recently used to assess inflammatory cells. We have previously reported an increased expression of Th-2–type cytokines in induced sputum of asthmatic patients. C-C chemokines, particularly eotaxin and monocyte chemotactic protein (MCP)-4, are associated with eosinophilic infiltration. Interleukin (IL)-16 is associated with chemotactic activity for CD4+ cells. Chemokine expression in BAL and bronchial biopsy specimens has been demonstrated in asthmatic airways, but not in induced sputum.

Methods: We examined whether eotaxin, MCP-4, and IL-16 expression could be detected in induced sputum of asthmatic patients (n = 10), and whether the expression was increased compared to normal control subjects (n = 9). Eotaxin, MCP-4, and IL-16 immunoreactivity were determined by immunocytochemistry. In addition, inflammatory cells were investigated using markers for T cells (CD3), eosinophils (major basic protein [MBP]), macrophages (CD68), neutrophils (elastase), and epithelial cells (cytokeratin).

Results: Our results showed that there was a significant difference in the percentages of MBP-positive and epithelial cells between asthmatic patients and normal control subjects (p < 0.05). However, there was no difference between these two groups in the percentage of CD3-, elastase-, and CD68-positive cells. Immunoreactivity for eotaxin, MCP-4, and IL-16 was expressed in the induced sputum of all asthmatic patients, and expression of these chemotactic cytokines was significantly greater than in control subjects (p < 0.001, p < 0.005, and p < 0.001, respectively).

Conclusions: This study showed that induced sputum could be used to detect chemokines in patients with bronchial asthma, and that the upregulation of chemotactic cytokines in the airways can be seen using noninvasive techniques.

Key Words: asthma • chemokines • induced sputum

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