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High Plasma Osteopontin Level and Its Relationship with Interleukin-12–mediated Type 1 T Helper Cell Response in Tuberculosis

First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa; Nagasaki Prefecture Tarami Hospital; Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki; Division of Molecular Immunology, Research Section of Molecular Pathogenesis, Institute for Genetic Medicine, Hokkaido University, Sapporo; Immuno-Biological Laboratories Co., Ltd., Gunma; National Okinawa Hospital, Ginowan; and Second Department of Internal Medicine, Oita Medical College, Oita, Japan

Correspondence and requests for reprints should be addressed to Dr. Kazuyoshi Kawakami, M.D., Ph.D., First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903–0215, Japan. E-mail: kawakami{at}med.u-ryukyu.ac.jp

Osteopontin (OPN, also known as Eta-1), a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in granulomatous lesions caused by Mycobacterium tuberculosis infection. In the present study, we compared plasma concentrations of OPN in patients with active pulmonary tuberculosis with those of healthy control subjects and patients with sarcoidosis, another disease associated with granuloma formation. Plasma OPN levels were significantly higher in patients with tuberculosis (n = 48) than in control subjects (n = 34) and patients with sarcoidosis (n = 20). OPN levels correlated well with severity of pulmonary tuberculosis, as indicated by the size of lung lesions on chest X-ray films. Furthermore, chemotherapy resulted in a significant fall in plasma OPN levels. In patients with tuberculosis, plasma OPN concentrations correlated significantly with those of interleukin (IL)-12. In vitro experiments showed that OPN production by peripheral blood mononuclear cells infected with Mycobacterium bovis bacillus Calmette–Guérin preceded the synthesis of IL-12 and interferon- and that the neutralizing anti-OPN monoclonal antibody significantly reduced the production of IL-12 and interferon-. Our results suggest that OPN may be involved in the pathologic process associated with active pulmonary tuberculosis by inducing IL-12–mediated type 1 T helper cell responses.

Key Words: osteopontin • interleukin-12 • tuberculosis • sarcoidosis • Mycobacterium bovis bacillus Calmette–Guérin

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