Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis.
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.
Shigehara
K
K
First Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. sigehara@za2.so-net.ne.jp
Shijubo
N
N
Ohmichi
M
M
Kamiguchi
K
K
Takahashi
R
R
Morita-Ichimura
S
S
Ohchi
T
T
Tatsuno
T
T
Hiraga
Y
Y
Abe
S
S
Sato
N
N
D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015622:Epithelioid Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000032:analysis / Q000097:blood*; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D018664:Interleukin-12 / Q000032:analysis / Q000097:blood*; D008168:Lung / Q000000981:diagnostic imaging / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011877:Radionuclide Imaging; D017565:Sarcoidosis, Pulmonary / Q000000981:diagnostic imaging / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D015415:Biomarkers; D007132:Immunoglobulin Isotypes; D018664:Interleukin-12; D007371:Interferon-gamma; D009113:Muramidase; D007703:Peptidyl-Dipeptidase A