J R Toro1, D Finlay, X Dou, S C Zheng, P E LeBoit, M K Connolly. 1. 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
Abstract
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.
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.
Authors: Kajal Hamidzadeh; Stephen M Christensen; Elizabeth Dalby; Prabha Chandrasekaran; David M Mosser Journal: Annu Rev Physiol Date: 2016-12-07 Impact factor: 19.318
Authors: Adam S Nabatian; Muhammad M Bashir; Maria Wysocka; Meena Sharma; Victoria P Werth Journal: Arthritis Res Ther Date: 2012-01-04 Impact factor: 5.156
Authors: José Ronaldo M Carneiro; Hellen T Fuzii; Cristiane Kayser; Fernando L Alberto; Fernando A Soares; Emília I Sato; Luís Eduardo C Andrade Journal: Clinics (Sao Paulo) Date: 2011 Impact factor: 2.365
Authors: Victoria P Werth; David Fiorentino; Barbara A Sullivan; Michael J Boedigheimer; Kit Chiu; Christine Wang; Gregory E Arnold; Michael A Damore; Jeannette Bigler; Andrew A Welcher; Chris B Russell; David A Martin; James B Chung Journal: Arthritis Rheumatol Date: 2017-03-31 Impact factor: 10.995