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Th1 and Th2 Cytokine mRNA Profiles in Childhood Nephrotic Syndrome

Evidence for Increased IL-13 mRNA Expression inRelapse

HUI-KIM YAP^*, WAI CHEUNG^*, BELINDA MURUGASU^*, SZE-KEEN SIM^*, CHING-CHING SEAH^* and STANLEY C. JORDAN

^* Department of Pediatrics, National University of Singapore, Singapore
Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California.

Correspondence to Dr. Hui-Kim Yap, Department of Pediatrics, National University of Singapore, Lower Kent Ridge Road, Singapore 119074. Phone: 65 772 4112; Fax: 65 779 7486; E-mail: paeyaphk{at}nus.edu.sg

Abstract. Idiopathic nephrotic syndrome of childhood is thought to be associated with T lymphocyte dysfunction often triggered by viral infections, with the production of circulating factor(s) resulting in proteinuria. In view of the conflicting evidence of T cell activation and Th1 or Th2 pattern of cytokine synthesis in this disease, this study examined the mRNA expression of interleukin-2 (IL-2), interferon-, IL-4, and IL-13 from CD4+ and CD8+ T cells in steroid-responsive nephrotic patients in relapse and remission. Fifty-five children with steroid-responsive nephrotic syndrome were included in this study, together with 34 normal controls and 24 patient controls with viral infections. RNA was isolated from purified CD4+ or CD8+ cells from peripheral blood and subjected to reverse transcription-PCR. Cytokine mRNA expression was measured semiquantitatively, and a cytokine index was derived from densitometric readings, with cyclophilin as the housekeeping gene. Both cross-sectional and paired data showed an increased CD4+ and CD8+ IL-13 mRNA expression in patients with nephrotic relapse as compared to remission, normal, and patient controls (P <0.008). This was also associated with increased cytoplasmic IL-13 expression in phorbol myristate acetate/ionomycin-activated CD3+ cells (6.66 ± 3.39%) from patients with nephrotic relapse compared to remission (2.59 ± 1.35%) (P < 0.0001). However, there was no significant difference in CD4+ or CD8+ IL-2, interferon- and IL-4 mRNA expression. IL-13 is an important T cell cytokine with anti-inflammatory and immunomodulatory functions on B cells and monocytes. It is conceivable that IL-13 may act on monocytes to produce vascular permeability factor(s) involved in the pathogenesis of proteinuria in patients with relapse nephrotic syndrome.

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