Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis
Open Access
- 24 March 2003
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 132 (1) , 152-157
- https://doi.org/10.1046/j.1365-2249.2003.02105.x
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‐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.Keywords
This publication has 24 references indexed in Scilit:
- Mice Lacking Bioactive IL-12 Can Generate Protective, Antigen-Specific Cellular Responses to Mycobacterial Infection Only if the IL-12 p40 Subunit Is PresentThe Journal of Immunology, 2002
- IL-12 and IL-18 Are Increased and Stimulate IFN-γ Production in Sarcoid LungsThe Journal of Immunology, 2001
- Statement on SarcoidosisAmerican Journal of Respiratory and Critical Care Medicine, 1999
- Characterization of mouse interleukin-12 p40 homodimer binding to the interleukin-12 receptor subunitsEuropean Journal of Immunology, 1999
- Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.The Journal of Experimental Medicine, 1996
- Serum p55 and p75 tumour necrosis factor receptors as markers of disease activity in juvenile chronic arthritis.Annals of the Rheumatic Diseases, 1996
- Expression of interferon-gamma (IFN-δ), IL-10, IL-12 and transforming growth factor-beta (TGF-β) mRNA in synovial fluid cells from patients in the early and late phases of rheumatoid arthritis (RA)Clinical and Experimental Immunology, 1996
- Interleukin 12 at the site of disease in tuberculosis.Journal of Clinical Investigation, 1994
- Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells.The Journal of Experimental Medicine, 1992
- Pitfalls in the Assay of Lysozyme in Human Tear FluidOphthalmic Research, 1977