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(Circulation. 2003;107:2196.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

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; 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.

Correspondence to Hirofumi Soejima, MD, PhD, Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto City 860-8556, Japan. 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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