IL-15 and IL-15R in leucocytes from patients with systemic lupus erythematosus

Objective. To assess the functional status of the IL-15/IL-15R alpha cytokine system in different leucocyte subsets from patients with systemic lupus erythematosus (SLE). Methods. Eighteen patients with SLE (10 with inactive and eight with active disease) and 14 healthy individuals were studied. Serum levels and in vitro production of IL-15 were determined. In addition, the expression of IL-15 receptor alpha (IL-15R alpha) and membrane-bound IL-15 was assessed and the in vitro effects of IL-15 on CD69 and CD64 expression, interferon-gamma and TNF-alpha synthesis, respiratory burst induction and apoptosis were studied. Results. Serum levels of IL-15 were significantly increased in inactive and active patients with SLE. Accordingly, the in vitro synthesis and release of IL-15 by monocytes in response to IFN-gamma+lipopolysaccharide was significantly enhanced in SLE patients with active disease, as was the percentage of membrane-bound IL-15(+) monocytes. On the other hand, enhanced basal expression of IL-15R alpha was detected in leucocytes from SLE patients, with defective induction upon stimulation with phytohaemagglutinin or phorbol myristate acetate/ionomycin. Furthermore, diminished induction of CD69 expression and interferon-gamma and TNF-alpha synthesis by recombinant human IL-15 was detected in peripheral blood mononuclear cells from SLE, and there was defective induction of CD64 and priming for respiratory burst in neutrophils. The anti-apoptotic effect of IL-15 was diminished in leucocytes from SLE patients. Conclusion. Our data indicate that there is enhanced synthesis of IL-15 by immune cells from SLE patients, with a poor response to this cytokine by different leucocyte subsets. This abnormal function of IL-15/IL-15R alpha may contribute significantly to the pathogenesis of SLE.