Table 1.
Studies on IL-12 and IL-12 receptors in sarcoidosis.
| Peripheral blood: | |||
|---|---|---|---|
| Method | Result | Reference | |
| ELISA | IL-12 p40 increased, IL-12p70 not detected (ELISA). | Shigehara et al. (2003),Hata et al. (2007) | |
| Antibody detection | IL-12Rβ2 not detected. | Rogge et al. (1999) | |
| mRNA, rtPCR | IL-12Rβ1 is elevated compared to healthy controls, but IL-12Rβ2 is not. | Judson et al. (2012) | |
| Granuloma lesions: | |||
| Affected organ | Method | Result | Reference |
| Skin | mRNA, rtPCR | IL-12p40, IL-12Rβ1 and IL-12Rβ2 are elevated compared to controls. | Judson et al. (2012) |
| Myocardium | IL12 ELISA and mRNA | IL-12 is elevated (antibody not specified). IL-12p40 and IL-12p35 mRNA are present but only IL12p40 significantly increased compared to dilated cardiomyopathy controls. | Terasaki et al. (2008) |
| Lung | Immunohistochemistry | IL12p70 is overexpressed by epithelioid cells and macrophages as well as giant cells. | Shigehara et al. (2001) |
| Lymph node | mRNA, rtPCR | IL-12p40 mRNA and IL-12Rβ2 mRNA is elevated, but not IL12p35 or IL-12Rβ1 | Hata et al. (2007) |
| Lung and lymph node | Immunohistochemistry | IL-12p40 is expressed by epithelioid cells and macrophages. | Shigehara et al. (2003) |
| Lymph node | mRNA | IL-12p40 is significantly increased compared to controls but not IL-12p35. | Bergeron et al. (1997) |
| BAL: | |||
| Method of detection | Result | Reference | |
| mRNA, ELISA | IL-12p40 mRNA and protein levels are significantly increased compared to healthy controls. BAL macrophages express higher levels of IL-12p70 both unstimulated and stimulated. | Moller et al. (1996) | |
| ELISA | IL-12p40 is elevated compared to healthy controls, but not IL-12p70. | Shigehara et al. (2001), Barbarin et al. (2003) | |
| Cytometric bead array | IL12p70 levels are significantly higher in patients compared to healthy controls. | Idali et al. (2006) | |
| ELISA (not specified) | IL-12 (not specified) is elevated compared to healthy controls. | Kim et al. (2000), Meloni et al. (2004), Antoniou et al. (2006), Mroz et al. (2008) | |
| FISH mRNA detection | IL-12p40 significantly elevated in patients with active sarcoidosis but not inactive sarcoidosis. | Minshall et al. (1997) | |
| mRNA | IL-12Rβ1 and IL-12Rβ2 levels are elevated in sarcoidosis patients. | Taha et al. (1999) | |
| Antibody detection | BAL cells of sarcoidosis patients express IL-12Rβ2. | Rogge et al. (1999) | |
| Stimulation assays with sarcoid antigens | |||
| Stimulus | Cells | Result | Reference |
| P. acnes | PBMC | IL-12p40 mRNA levels are significantly elevated in sarcoidosis patients compared to healthy controls. | Furusawa et al. (2012) |
| β-glucan/LPS | PBMC | Spontaneous and post-stimulation IL-12 protein levels are higher in patients compared to controls (IL 12 ELISA not further specified). | Rastogi et al. (2011) |
| NOD1/TLR4 ligands | BALF | IL12/23 p40 protein and mRNA levels are increased compared to healthy controls. | Rastogi et al. (2011) |
Multiple studies confirm IL-12p40 and IL-12Rβ1 up-regulation in peripheral blood, BAL, and granulomatous tissue, while the corresponding IL-12p35 is not dysregulated and IL-12p70 (the functional IL-12 protein) in most studies not detectable.