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The pathogenesis of systemic sclerosis (SSc) is characterized by autoimmunity, vasculopathy and fibrosis. IL-15 is a pleiotropic cytokine that has impact on immune, vascular and connective tissue cells. We therefore investigated IL-15 in the circulation of patients with early SSc and explored possible associations of serum IL-15 with vasculopathy and fibrosis. Serum levels of IL-15 were analysed in 63 consecutive patients with SSc of disease duration less than 4 years and without disease-modifying treatment. Thirty-three age-matched healthy control individuals were enrolled. Serum IL-15 levels were increased in the sera of SSc patients compared with that of healthy control individuals ( P  < 0.01). Serum IL-15 levels correlated with impaired lung function, assessed both by the vital capacity ( P  < 0.05) and by the carbon monoxide diffusion capacity ( P  < 0.05). The association between IL-15 and the vital capacity remained after multiple linear regression analysis. Patients with intermediate serum IL-15 levels had a higher prevalence of increased systolic pulmonary pressure compared with patients with either low or high serum IL-15 levels ( P  < 0.05). Moreover, increased serum IL-15 levels were associated with a reduced nailfold capillary density in multivariable logistic regression analysis ( P  < 0.01). Serum IL-15 levels also correlated inversely with the systolic blood pressure ( P  < 0.01). We conclude that IL-15 is associated with fibrotic as well as vascular lung disease and vasculopathy in early SSc. IL-15 may contribute to the pathogenesis of SSc. IL-15 could also be a candidate biomarker for pulmonary involvement and a target for therapy in SSc.

Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease