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Detection of type 1 cytokines in discoid lupus erythematosus
1National Cancer Intitute, National Institutes of Health, Building 10, Room 12N-238, 10 Center Dr, MSC 1908, Bethesda, MD 20892-1908, USA. torojo@exchange.nih.gov
Background:
Although multiple studies suggest a dysregulated T-cell cytokine production in systemic lupus erythematosus, the cytokine profile in discoid lupus erythematosus (DLE) lesions is unknown.
Objectives:
To characterize the cytokine profile in DLE by immunohistochemical and molecular methods, and to investigate the role of cytokines in the pathogenesis of DLE.
Design:
Patients were evaluated clinically, and biopsy specimens of lesional skin were examined by light microscopy. Reverse transcriptase-polymerase chain reaction and immunohistochemical analysis were performed on 11 biopsy specimens. We investigated the presence of interleukin (IL) 2, interferon gamma (IFN-gamma), IL-4, tumor necrosis factor alpha, (TNF-alpha), and IL-1beta messenger RNA (mRNA) in 8 biopsy specimens of DLE and compared it with 3 biopsy specimens of normal skin.
Setting:
Academic referral research hospital.
Patients:
Eight consecutive patients with a clinical and histologic diagnosis of DLE.
Results:
Localized DLE was found in 7 patients and widespread in 1. During the 4 years of the investigation, none of the patients developed systemic lupus erythematosus. We found significantly elevated levels of IL-2 and IFN-gamma mRNA in all 8 biopsy specimens of DLE; in contrast, no transcripts of IL-2 or IFN-gamma were detected in 3 biopsy specimens of normal skin (P<.01). Similarly, elevated levels of TNF-alpha mRNA were detected in 8 DLE biopsy specimens, while no TNF-alpha mRNA was detected in 3 biopsy specimens of normal skin (P<.01). No IL-4 or IL-1 beta mRNA was detected in 8 biopsy specimens of DLE lesional skin and 3 biopsy specimens of normal patient skin. Immunohistochemical analysis showed increased staining for IL-2 and IFN-gamma receptors, while no detectable IL-4 receptor was found. No cytokine mRNA or cytokine receptor protein was detected in biopsy specimens of normal skin.
Conclusions:
These findings suggest that DLE is associated with type 1 cytokines characterized by the expression of IL-2 and IFN-gamma. Type 1 cytokines may be critical for induction, development, and maintenance of DLE.