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Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis

  1. K. SHIGEHARA1,3,*,
  2. N. SHIJUBO2,4,
  3. M. OHMICHI4,
  4. K. KAMIGUCHI1,
  5. R. TAKAHASHI2,4,
  6. S. MORITA-ICHIMURA2,4,
  7. T. OHCHI2,
  8. T. TATSUNO3,
  9. Y. HIRAGA4,
  10. S. ABE2,
  11. N. SATO1

Article first published online: 24 MAR 2003

DOI: 10.1046/j.1365-2249.2003.02105.x

Issue

Clinical & Experimental Immunology

Clinical & Experimental Immunology

Volume 132, Issue 1, pages 152–157, April 2003

Additional Information

How to Cite

SHIGEHARA, K., SHIJUBO, N., OHMICHI, M., KAMIGUCHI, K., TAKAHASHI, R., MORITA-ICHIMURA, S., OHCHI, T., TATSUNO, T., HIRAGA, Y., ABE, S. and SATO, N. (2003), Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis. Clinical & Experimental Immunology, 132: 152–157. doi: 10.1046/j.1365-2249.2003.02105.x

Author Information

  1. 1

    First Department of Pathology and

  2. 2

    Third Department of Internal Medicine, Sapporo Medical University School of Medicine,

  3. 3

    Hokkaido Branch of Japan Anti-tuberculosis Association, and

  4. 4

    Department of Respiratory Disease of Sapporo Hospital, Hokkaido Railway Company, Sapporo, Japan

* Katsunori Shigehara, First Department of Pathology, Sapporo Medical University School of Medicine South-1, West-17, Chuo-ku, Sapporo 060–8556, Japan.   E-mail: sigehara@za2.so-net.ne.jp

Publication History

  1. Issue published online: 24 MAR 2003
  2. Article first published online: 24 MAR 2003
  3. (Accepted for publication 5 January 2003)

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Keywords:

  • IL-12 p40;
  • Th1 predominance;
  • pulmonary sarcoidosis

SUMMARY

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-γ (IFN-γ) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-γ. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.

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