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-gamma (IFN-gamma) 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-gamma. 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.