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Influence of Functional Interleukin 10/Tumor Necrosis Factor-α Polymorphisms on Interferon-α, IL-10, and Regulatory T Cell Population in Patients with Systemic Lupus Erythematosus Receiving Antimalarial Treatment

PATRICIA LÓPEZ, JESÚS GÓMEZ, CATUXA PRADO, CARMEN GUTIÉRREZ, and ANA SUÁREZ

ABSTRACT.

Objective. As interleukin 10 (IL-10)/tumor necrosis factor-α (TNF-α) polymorphisms have been shown to influence TNF-α inhibition and clinical response to antimalarial treatment in patients with systemic lupus erythematosus (SLE), we investigated involvement of these variants in antimalarial effects on cytokine serum levels and regulatory T cell population (Treg).

Methods. The alleles present at –308 TNF-α and –1082 IL-10 genes; serum concentrations of interferon-α (IFN-α), IL-10 and TNF-α; and size and function of CD4+CD25^high (Treg) population were determined in SLE patients and in healthy controls. These data were related to treatment and clinical manifestations.

Results. Patients were observed to have increased IFN-α serum levels that did not correlate with any treatment. Among patients receiving antimalarial drugs, high IL-10/low TNF-α producers presented higher levels of IFN-α and IL-10 than carriers of other genotypes. In contrast, patients with the converse, low IL-10/high TNF-α genotype who were receiving antimalarial treatment presented increased size and function of Treg population. The percentage of CD4+CD25^high cells was inversely correlated to TNF-α levels.

Conclusion. Our findings suggest that the beneficial effect of antimalarials in low IL-10/high TNF-α patients with SLE may be partially attributable to the increase in Treg activity, whereas patients with the converse genotype did not show this phenomenon, yet did have significantly upregulated levels of IFN-α and IL-10, 2 cytokines that have been associated with SLE activity. (First Release June 15 2008; J Rheumatol 2008;35:1559–66)

Key Indexing Terms:

SYSTEMIC LUPUS ERYTHEMATOSUS
ANTIMALARIALS
CYTOKINES
SINGLE-NUCLEOTIDE POLYMORPHISMS
REGULATORY T LYMPHOCYTES

From the Department of Functional Biology, Immunology Area, University of Oviedo; and Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.

Supported by Grant PI052409 from the Fondo de Investigación Sanitaria. Ms López was supported by a grant from the Fundación Eugenio Rodríguez Pascual.

P. López, BSc, Department of Functional Biology, Immunology Area, University of Oviedo; J. Gómez, MD, Department of Immunology, Hospital Universitario Central de Asturias; C. Prado, BSc, Department of Functional Biology, Immunology Area, University of Oviedo; C. Gutiérrez, PhD, Department of Functional Biology, Immunology Area, University of Oviedo and Department of Immunology, Hospital Universitario Central de Asturias; A. Suárez, PhD, Department of Functional Biology, Immunology Area, University of Oviedo.

Address reprint requests to Dr. A. Suárez, Department of Functional Biology, Immunology Area, Facultad de Medicina, Julián Clavería s/n 33006 Oviedo, Spain. E-mail: anasua@uniovi.es

Accepted for publication March 10, 2008.