interleukin-8 and Scleroderma--Localized

In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro-inflammatory cytokines have been demonstrated at increased levels in sera of patients with LS in parallel with disease activity. Human beta-defensins (hBDs) are peptides with antimicrobial activity, but have been also shown to be implicated in tissue injury, scarring and wound healing. hBD expression in LS, a condition resembling pathological scarring due to excessive stimulation of matrix synthesis and fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1 phototherapy, the most recent advance in the treatment of LS, targets T-cell dermal inflammatory infiltrates via induction of various cytokines and soluble factors besides well-known effects on collagen metabolism.. We sought to investigate the effects of UVA1 on the expression and modulation of hBDs and several pro-inflammatory cytokines in LS.. UVA1 phototherapy was performed five times weekly for 8 weeks resulting in a total of 40 treatment sessions (single dose 20 J cm2, cumulative dose 800 J cm2). hBD-1, hBD-2 and hBD-3 mRNA as well as tumour necrosis factor-alpha, transforming growth factor-beta, interleukin (IL) -2, IL-4, IL-6 and IL-8 mRNA expression were determined by quantitative real-time reverse transcription-polymerase chain reaction in lesional and unaffected skin of patients with LS.. Skin status markedly improved in all 14 patients, resulting in a significant reduction of the clinical score from baseline to the end of treatment. hBD-1, hBD-2 and hBD-3 mRNA levels were higher in lesional skin compared with unaffected skin and skin from healthy volunteers. Following UVA1 phototherapy, hBD-1 mRNA decreased in lesional, but not in unaffected skin. hBD-3 mRNA levels significantly decreased after UVA1 in lesional skin, whereas an increase of hBD-3 was observed in unaffected skin. IL-6 and IL-8 mRNA levels were significantly elevated in lesional skin and significantly decreased after UVA1 irradiation, whereas mRNA for both cytokines remained unchanged in irradiated unaffected skin. The decrease of hBD-1, hBD-3, IL-6 and IL-8 mRNA paralleled the extent of disease and response to UVA1 phototherapy.. hBDs and IL-6 and IL-8, cytokines with pivotal importance in sclerotic skin diseases, are downregulated by UVA1 in the lesional skin of patients with LS. Their pathogenetic relevance with respect to clinical improvement needs further investigation.

Topics: Adult; beta-Defensins; Down-Regulation; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Scleroderma, Localized; Severity of Illness Index; Skin; Treatment Outcome; Ultraviolet Therapy

Topics: Case-Control Studies; Humans; Interleukin-8; Scleroderma, Localized; Scleroderma, Systemic

Interleukin 8 (IL-8), a chemotactic cytokine produced by various cell types, displays structural homology to the connective tissue-activating peptide III. Little is known of the possible role of IL-8 in connective tissue disorders. We therefore determined serum concentrations of IL-8 and autoantibodies to IL-8 in 134 patients with systemic sclerosis (SSc) and related connective tissue disorders, as well as in pooled serum from 28 healthy control subjects by a sensitive enzyme-linked immunosorbent assay.. Interleukin 8 was undetectable in the pooled serum from 28 healthy controls, but detectable in serum samples from 24 of the 134 patients described above. It was detected in 13 of 60 patients with limited SSc and in eight of 48 patients with diffuse SSc. It was also detectable in one of three patients with eosinophilic fasciitis and in two of 10 patients with Raynaud's syndrome without skin involvement. In contrast, none of the three patients with morphea or the 10 patients with eosinophilia-myalgia syndrome had detectable IL-8 levels. We further determined the concentration of autoantibodies to IL-8 in the same serum samples. The values in healthy controls were 6.7 +/- 0.2 ng/mL (mean +/- SEM). Significantly elevated autoantibody levels were detected in patients with limited SSc (21.5 +/- 1.7), diffuse SSc (23.4 +/- 2.2), and Raynaud's syndrome (20.5 +/- 3.7). Elevated levels were also detected in patients with eosinophilic fasciitis (43.7 +/- 8.6) and morphea (14.7 +/- 3.2). Normal levels (7.5 +/- 2.0) were found in patients with eosinophilia-myalgia syndrome. Analysis of variance between the levels of autoantibodies to IL-8 and duration of the disease, extent of skin involvement, drug therapy, or serologic findings failed to show a significant correlation.. These results suggest that increased production of IL-8 may relate to activation of mononuclear phagocytes, fibroblasts, or endothelial cells, among other cell types, in patients with SSc, but not in those with eosinophilia-myalgia syndrome. This activation could be related to the production of autoantibodies to IL-8.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Connective Tissue Diseases; Eosinophilia; Eosinophilia-Myalgia Syndrome; Fasciitis; Female; Humans; Interleukin-8; Male; Middle Aged; Raynaud Disease; Regression Analysis; Scleroderma, Localized; Scleroderma, Systemic