Background and design: 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.
Results: 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.
Conclusions: 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.