Increased IL-2, IL-4 and interferon-gamma (IFN-γ) in steroid-sensitive nephrotic syndrome

Abstract

SUMMARYWe investigated the production of cytokines by peripheral blood mononuclear cells (PBMC) and serum cytokine concentrations in children with steroid-sensitive idiopathic nephrotic syndrome (SSNS). PBMC from patients off treatment were collected during remission and relapse and cultured in medium alone or stimulated with calcium ionophore plus phorbol myristate acetate. Control PBMC were taken from healthy age-matched children. IL-2 was measured by bioassay, IL-4 by immunoradiometric assay, and IL-8 and IFN-7 by ELISA. After 24 h culture without stimulation, IL-2, IL-4 and IFN-7 were not detectable in the supernatant in any of the children. After stimulation, the supernatant concentrations of IL-2 (median 172 U/ml at 24 h) and IL-4 (160pg/ml at 24 h; 210pg/ml at 72 h) were significantly increased in relapse compared with remission (IL-2 37 U/ml; IL-4 65pg/ml and 60pg/ml) and controls (IL-2 69 U/ml; IL-4 40pg/ml and 40pg/ml) (/'<0-05). The concentration of IFN-7 was not significantly increased in relapse compared with remission and controls (600, 325, and 145 U/ml, respectively, at 72 h). lL-8 concentrations were similar in relapse, remission and controls with stimulation (median 32, 40 and 40 ng/ml, respectively) and without (30, 17 and 10 ng/ml). IL-2 was not detectable in serum, but IL-4, IL-8 and IFN-7 were measurable in about half the patients, both in relapse and remission, though were virtually undetectable in controls. We conclude that relapse of SSNS in children is associated with T lymphocyte activation with release of IL-2, IL-4 and IFN-7.

T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS

“…This was in contrast to the published study by Gulati et al (4), in which patients with late steroid + expression in FSGS rituximab responders compared with those in both nonresponders and controls, and it was associated with significantly reduced mitogen-stimulated CD3 production of IFN-g and IL-2. The baseline immunologic signature in our FSGS rituximab responders was also significantly different from that in patients with MCNS in relapse as shown in Table 3, indicating that the immunologic basis underlying the nephrotic syndrome is likely to be distinct in this group of FSGS rituximab responders compared with those in patients with MCNS, in whom increased mitogen-stimulated lymphocyte production of IL-2 and IFN-g has been shown (27)(28)(29)(30)(31).…”

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

“…A potential candidate for a permeability factor is IL-8/CXCL8. Most studies that assessed this chemokine in INS found increased serum levels in patients during relapse, and normal concentrations in remission (7,8,38). IL-8/CXCL8 was also found to have effects on the metabolism of the glomerular basement membrane, possibly increasing glomerular permeability (7).…”

Cytokine Gene Polymorphism in Idiopathic Nephrotic Syndrome Children

“…Stimuli, such as allergens, may activate common immune mechanisms, which subsequently result in proteinuria in children with MCNS. Several investigators have demonstrated the potential role of Th2 cytokines in this disease [3][4][5][6].…”