IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions

Abstract

OBJECTIVE:To analyze cytokine gene expression in keratinocytes from patients with systemic lupus erythematosus (SLE).INTRODUCTION:Keratinocytes represent 95% of epidermal cells and can secrete several cytokines.METHODS:Keratinocytes were obtained by laser microdissection from 21 patients with SLE (10 discoid and 11 acute lesions) at involved and uninvolved sites. All patients were receiving a low/moderate prednisone dose and 18 were receiving chloroquine diphosphate. IL-2, IL-5, TNF-α and IFN-γ gene expression was evaluated by real-time PCR and expressed as the ratio (R) to a pool of skin samples from 12 healthy volunteers.RESULTS:Heterogeneity in cytokine gene expression was found among patients with SLE. Eighteen of 38 valid SLE samples (47%) presented overexpression (R>1) of at least one cytokine. Lesional skin samples tended to show higher cytokine expression than samples from uninvolved skin (p = 0.06). IL-5 and IFN-γ were the most commonly overexpressed cytokines. Samples with cytokine overexpression corresponded to more extensive and severe lesions. Prednisone dose did not differ between samples without cytokine overexpression (15.71±3.45 mg/day) and those with overexpressed cytokines (12.68±5.41 mg/day) (p = 0.216). Samples from all patients not receiving diphosphate chloroquine had at least one overexpressed cytokine.CONCLUSIONS:The heterogeneous keratinocyte cytokine gene expression reflects the complex immunological and inflammatory background in SLE. Patients with severe/extensive skin lesions showed a higher frequency of cytokine gene overexpression. Increased IFN-γ and IL-5 expression suggests that Th1 and Th2 cells are involved in SLE skin inflammation. The possibility that prednisone and antimalarial drugs may have contributed to low cytokine gene expression in some samples cannot be ruled out.

Scavenging nucleic acid debris to combat autoimmunity and infectious disease

“…This in turn results in further downstream activation of signaling pathways and production of proinflammatory cytokines (15,40). In fact, multiple autoimmune disorders are characterized by elevated levels of circulating proinflammatory cytokines and autoantibodies (41)(42)(43). To date, numerous studies and clinical trials have focused on addressing circulating self-RNA and DNA, TLR activation, proinflammatory cytokines and circulating autoantibodies (16).…”

Kinetic Cytokine Secretion Profile of LPS-Induced Inflammation in the Human Skin Organ Culture

“…Interestingly, IL-15 and IL-10, which are secreted by T helper cells as well, are also produced by keratinocytes and dendritic cells in the skin [4], and are accordingly detected in the activated spent media (Figure 2). It should be noted that IL-2 and IL-5 were reportedly detected, at the transcriptome level, in keratinocytes from healthy and lupus human skin in the minority of individuals [37]. Such publications, however, are rare.…”

T cell subsets and their signature cytokines in autoimmune and inflammatory diseases

“…It is possible that IL-5 may have an immunomodulatory function in MS, as relapsing-remitting MS patients treated with glatiramer acetate (Copaxone) showed reduced relapse frequency with a concomitant increase in IL-5 producing T cells 91 . In SLE patients with severe skin involvement, IFN-γ and IL-5 were the most commonly overexpressed cytokines in skin lesions, implying that both Th1 and Th2 subsets may be involved in the pathophysiology of SLE inflammation 92 . However, an earlier report suggests that IL-5 may play a protective role as overexpression of IL-5 in SLE-prone mice suppresses the disease 93 .…”