Published Online
on April 14, 2003

A more recent version of this article appeared on May 6, 2003

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Submitted on November 11, 2002
Revised on February 12, 2003
Accepted on February 18, 2003

Preference Toward a T-Helper Type 1 Response in Patients With Coronary Spastic Angina

Hirofumi Soejima MD, PhD^*, Atsushi Irie PhD, Shinzo Miyamoto MD, Ichiro Kajiwara MD, Sunao Kojima MD, Jun Hokamaki MD, Tomohiro Sakamoto MD, PhD, Tomoko Tanaka MD, Michihiro Yoshimura MD, PhD, Yasuharu Nishimura MD, PhD, and Hisao Ogawa MD, PhD

From the Department of Cardiovascular Medicine (H.S., S.M., I.K., S.K., J.H., T.S., T.T., M.Y., H.O.) and Department of Neuroscience Immunology (A.I., Y.N.), Kumamoto University School of Medicine, Kumamoto, Japan.

^* To whom correspondence should be addressed. E-mail: yuuki{at}gpo.kumamoto-u.ac.jp.

Background--Coronary artery spasm plays an important role in the pathogenesis of ischemic heart diseases such as unstable angina (UA) and acute myocardial infarction. Nitric oxide (NO) plays an important role in coronary artery spasm. We previously reported a deficiency in NO activity in the spasm arteries of patients with coronary spastic angina (CSA). Others have reported that NO influences the immune response. Therefore, we investigated the balance between T-helper type 1 (Th1) and 2 (Th2) responses in patients with CSA by evaluating the frequencies of interferon (IFN)--producing T cells and interleukin (IL)-4-producing T cells in the peripheral blood of such patients.

Methods and Results--Peripheral blood mononuclear cells were collected from 50 consecutive patients with CSA, 23 consecutive patients with UA, 36 patients with stable angina (SA), and 21 patients with chest pain syndrome (CPS). Cytokine-producing CD4+ T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA and CSA were associated with a significant increase in the frequency of CD4+ T cells that produced IFN-, whereas these conditions caused no significant difference in the frequency of CD4+ T cells that produced IL-4. Culturing with an NO donor compound for 24 hours before stimulation inhibited the increase in the frequency of CD4+ T cells that produced IFN-.

Conclusions--We demonstrated that there was a preference toward the Th1-type response in patients with CSA and that T cells showed a reduced Th1-type response after being treated with NO.

Key words: vasospasm • inflammation • lymphocytes

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