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Rheumatology Advance Access published online on October 26, 2005
Rheumatology, doi:10.1093/rheumatology/kei083
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received May 31, 2005
Accepted July 19, 2005

Original Papers

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

L. Baranda 1, H. de la Fuente 2, E. Layseca-Espinosa 3, D. Portales-Pérez 4, P. Niño-Moreno 3, G. Valencia-Pacheco 3, C. Abud-Mendoza 4, J. Alcocer-Varela 5, and R. González-Amaro 3*

1 Departamento de Inmunología, Facultad de Medicina, UASLP, San Luis Potosí, SLP, México; Unidad Regional de Reumatología y Osteoporosis Hospital Central Dr Ignacio Morones PrietoUASLP, San Luis Potosí, SLP, México; L.B. and H. de la F. contributed equally to this work
2 Departamento de Inmunología, Facultad de Medicina, UASLP, San Luis Potosí, SLP, México; L.B. and H. de la F. contributed equally to this work
3 Departamento de Inmunología, Facultad de Medicina, UASLP, San Luis Potosí, SLP, México
4 Laboratorio de Inmunología, Facultad de Ciencias Químicas, UASLP, San Luis Potosí, SLP, México
5 Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y de la Nutrición Salvador Zubirán, México, DF, México

* To whom correspondence should be addressed.
R. González-Amaro, E-mail: rgonzale{at}uaslp.mx


  Abstract

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.

Keywords: Cytokines; Autoimmunity; Apoptosis; CD69; Lymphocytes.
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