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Kinins and Cytokines in Plasma and Cerebrospinal Fluid of Patients with Neuropsychiatric Lupus
RENATA DELLALIBERA-JOVILIANO, MARINA LEMOS DOS REIS, FERNANDO DE QUEIROZ CUNHA, and EDUARDO ANTONIO DONADI
ABSTRACT. Methods. We studied 29 women with active NPL and 29 healthy women matched to patients for age. Low (LKg) and high molecular weight kininogen (HKg) and cytokine concentrations [interleukin 1ß (IL-1ß), IL-6, IL-8, IL-10, and tumor necrosis factor-a (TNF-a)] were determined by ELISA. The activities of tissue kallikrein, plasma prekallikrein, and kininase II were assayed by their action on selective substrates. Results. Compared to controls, patients with NPL presented increased plasma and CSF levels of LKg, HKg, and prekallikrein, increased activity of tissue kallikrein and kininase II, and increased levels of IL-6, IL-10, and TNF-a (p < 0.001 each comparison). IL-1ß levels were increased in patient plasma (p < 0.001), whereas plasma IL-8 levels did not differ from controls. IL-1ß and IL-8 were not detected in CSF of patients or controls. Conclusion. The increased levels of kininogen fractions, kallikreins, and kininase II in patient plasma and CSF indicate overactivity of the kinin system, suggesting intense kinin production. Since kinins may induce the production of proinflammatory cytokines including IL-1ß, IL-6, and TNF-a, these findings support the participation of kinins and cytokines in the acute manifestations of NPL. Most of the variables evaluated in patients' CSF increased proportionally in relation to plasma levels. In contrast, the activity of tissue kallikrein in patient CSF increased out of proportion to plasma levels, appearing to be locally synthesized in response to brain involvement. (J Rheumatol 2003;30:485-92) Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS
From the Departments of Medicine and Pharmacology, Basic and Applied Immunology Program, Faculty of Medicine; and Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil. Supported by grants from Fundação de Apoio à Pesquisa do Estado do São Paulo (FAPESP; grant 00-03684-8) and Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FAEPA). R. Dellalibera-Joviliano, MSc, Basic and Applied Immunology Program, Faculty of Medicine of Ribeirão Preto; F.Q. Cunha, PhD, Department of Pharmacology, Faculty of Medicine of Ribeirão Preto; M.L. Reis, PhD, Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto; E.A. Donadi, MD, PhD, Division of Clinical Immunology, Department of Medicine, Faculty of Medicine of Ribeirão Preto. Address reprint requests to Dr. E.A. Donadi, Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo - USP, Avenida Bandeirantes 3900, Monte Alegre, 14049-900, Ribeirão Preto, SP, Brazil. E-mail: eadonadi@fmrp.usp.br Submitted February 21, 2002; revision accepted August 19, 2002. |