Background Corticotropin-releasing hormone (CRH) and the pro-opiomelanocortin (POMC) axis activation leads to the production of several bioactive hormones such as adrenocorticotrophic hormone (ACTH) and the neuropeptide α-melanocyte stimulating hormone (α-MSH). In systemic lupus erythematosus (SLE), the prototype of autoimmune disease with a high frequency of skin involvement. There are no data concerning the possible role of CRH and MCs in the physiopathology of its cutaneous lesions.
Objectives Thus, the aim of the present study was to evaluate if CRH and POMC axis activation underlies the cutaneous inflammatory response in SLE patients
Methods Seventeen SLE patients were clinically evaluated and biopsies from affected and unaffected skin were compared to 17 healthy subjects. Immunohistochemical analysis for CRH, ACTH, a-MSH, and MC-1R were performed. Cytokine serum levels (IL-1, IL-1Ra, IL-6, IL-10, IL-12p70, IL-17, TNF-a, IFN-γ) was evaluated by multiplex bead-based immunoassay.
Results Interestingly, affected skin of SLE patients exhibited higher CRH expression in the deep dermis compared to controls (figure, p=0.024), in contrast, no difference regarding CRH expression in the epidermis was observed comparing affected and unaffected skin of SLE patients and health skin (p=0.353). Tissue expression of ACTH, cortisol, a-MSH and its receptor MC-1R were comparable in SLE and controls. Significantly higher serum levels of IFN-g (p=0.041), TNF-a (p=0.001) and IL-6 (p=0.049) were observed in SLE while a-MSH serum levels were alike in both groups.
Conclusions The novel finding of elevated CRH expression solely in affected skin deep dermis supports the notion of a cutaneous local dysfunction of CRH-POMC axis in the pathogenesis of cutaneous SLE lesions.
Acknowledgements Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #09/54549-8)
Disclosure of Interest None declared
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