title: Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis.
abstract: 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.
authors.affiliation: First Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. sigehara@za2.so-net.ne.jp
authors.forename: K
authors.initials: K
authors.lastname: Shigehara
authors.forename: N
authors.initials: N
authors.lastname: Shijubo
authors.forename: M
authors.initials: M
authors.lastname: Ohmichi
authors.forename: K
authors.initials: K
authors.lastname: Kamiguchi
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Morita-Ichimura
authors.forename: T
authors.initials: T
authors.lastname: Ohchi
authors.forename: T
authors.initials: T
authors.lastname: Tatsuno
authors.forename: Y
authors.initials: Y
authors.lastname: Hiraga
authors.forename: S
authors.initials: S
authors.lastname: Abe
authors.forename: N
authors.initials: N
authors.lastname: Sato
mesh_terms: 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*
chemical_list: D015415:Biomarkers; D007132:Immunoglobulin Isotypes; D018664:Interleukin-12; D007371:Interferon-gamma; D009113:Muramidase; D007703:Peptidyl-Dipeptidase A