Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: Evidence for increased IL-13 mRNA expression in relapse

Idiopathic nephrotic syndrome of childhood is thought to be associated with T lymphocyte dysfunction often triggered by viral infections, with the pro duction of circulating factor(s) resulting in proteinuria. In view of the c onflicting evidence of T cell activation and Th1 or Th2 pattern of cytokine synthesis in this disease, this study examined the mRNA expression of inte rleukin-2 (IL-2), interferon-gamma, IL-4, and IL-13 from CD4+ and CD8+ T ce lls in steroid-responsive nephrotic patients in relapse and remission. Fift y-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 pe ripheral blood and subjected to reverse transcription-PCR. Cytokine mRNA ex pression was measured semiquantitatively, and a cytokine index was derived from densitometric readings, with cyclophilin as the house-keeping gene. Bo th 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 i ncreased cytoplasmic IL-13 expression in phorbol myristate acetate/ionomyci n-activated CD3+ cells (6.66 +/- 3.39%) from patients with nephrotic relaps e compared to remission (2.59 +/- 1.35%) (P < 0.0001). However, there was n o significant difference in CD4+ or CD8+ IL-2, interferon-gamma and IL-4 mR NA 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 nephr otic syndrome.