Detection of type 1 cytokines in discoid lupus erythematosus.
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.


OBJECTIVE
To characterize the cytokine profile in DLE by immunohistochemical and molecular methods, and to investigate the role of cytokines in the pathogenesis of DLE.


METHODS
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.


METHODS
Academic referral research hospital.


METHODS
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.
Toro
J R
JR
National 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
Finlay
D
D
Dou
X
X
Zheng
S C
SC
LeBoit
P E
PE
Connolly
M K
MK
D000328:Adult; D015331:Cohort Studies; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis*; D007376:Interleukin-2 / Q000032:analysis*; D008179:Lupus Erythematosus, Discoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D007376:Interleukin-2; D007371:Interferon-gamma