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Published ahead of print on February 5, 2003, doi:10.1164/rccm.200209-1113OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 10, May 2003, 1355-1359

A more recent version of this article appeared on May 15, 2003
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Submitted on October 22, 2002
Accepted on January 24, 2003

High plasma osteopontin level and its relationship with IL-12-mediated Th1 response in tuberculosis

Yoshinobu Koguchi1, Kazuyoshi Kawakami1*, Kaori Uezu1, Kiyoyasu Fukushima2, Sigeyuki Kon3, Masahiro Maeda4, Atsushi Nakamoto5, Isoko Owan5, Mutsuo Kuba5, Norifumi Kudeken1, Jun-Ichi Kadota6, Hiroshi Mukae7, Shigeru Kohno7, Toshimitsu Uede3, and Atsushi Saito1

1 First Department of Internal Medicine, University of the Ryukyus, Okinawa, Japan, 2 Nagasaki Prefecture Tarami Hospital, Nagasaki, Japan, 3 Division of Molecular Immunology, Research Section of Molecular Pathogenesis, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan, 4 Immuno-Biological Laboratories Co., Ltd.,, Gunma, Japan, 5 National Okinawa Hospital, Ginowan, Japan, 6 Second Department of Internal Medicine, Oita Medical College, Oita, Japan, 7 Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan

* To whom correspondence should be addressed. 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 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 M. bovis BCG preceded the synthesis of IL-12 and interferon (IFN)-{gamma}, and that neutralizing anti-OPN monoclonal antibody significantly reduced the production of IL-12 and IFN-{gamma}. Our results suggest that OPN may be involved in the pathological process associated with active pulmonary tuberculosis by inducing IL-12-mediated Th1 responses.
Key words: osteopontin, IL-12, tuberculosis, sarcoidosis, Mycobacterium bovis BCG




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