IL-15 and IL-15R in leucocytes from patients with systemic lupus erythematosus.
OBJECTIVE: To assess the functional status of the IL-15/IL-15Ralpha 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-15Ralpha) 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-15Ralpha 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-15Ralpha may contribute significantly to the pathogenesis of SLE.[1]References
- IL-15 and IL-15R in leucocytes from patients with systemic lupus erythematosus. Baranda, L., de la Fuente, H., Layseca-Espinosa, E., Portales-Pérez, D., Niño-Moreno, P., Valencia-Pacheco, G., Abud-Mendoza, C., Alcocer-Varela, J., González-Amaro, R. Rheumatology (Oxford, England) (2005) [Pubmed]
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