T-lymphocyte populations, cytokines and other growth factors in serum and urine of children with idiopathic nephrotic syndrome.

The T-cell defect present in the idiopathic nephrotic syndrome (INS) was investigated in 29 steroid-sensitive and 14 steroid-resistant children aged 2-19 years. Nine different lymphocyte subpopulations and 15 cytokines, receptors and other growth factors were measured in blood, and some also in urine. In steroid-sensitive patients we found a decreased ratio of helper/inducer cells (CD4+) versus suppressor/cytotoxic cells (CD8+) in relapse and remission, and an increased proportion of natural killer cells (CD16+) during relapse vs long-term remission, as a sign of an elevated cytotoxic potential. Among the serum cytokines mainly produced by monocytes/macrophages interleukin (IL)-8 levels were decreased in steroid-sensitive patients vs controls, with normal levels observed for IL-1 alpha, IL-1 beta, IL-1RA and tumor necrosis factor (TNF-alpha). IL-2 was the only cytokine produced by TH1 cells which was significantly increased during relapse vs long-term remission. We also observed a trend for elevated levels of sIL-2R and IFN-gamma. Serum levels of cytokines derived from TH2 cells were variable. IL-4 was decreased during relapse but increased in patients with long-term remission. SIL-6 receptors were increased during relapse. Finally we observed decreased serum levels of IL-3 and of the adhesion molecule ICAM-1 in active INS. Patients with steroid-resistant INS exhibited similar changes of T-cell populations and cytokines as steroid-sensitive patients; their CD4+/CD8+ ratio was reduced to the same degree and sIL-2R levels were even higher than in steroid-sensitive patients. In conclusion this study indicates that active INS is associated with an increased number of cytotoxic cells in the blood and an elevated TH1 cytokine production. Long-term remission appears to be related to increased TH2 cytokine production downregulating TH1 cytokines and cytotoxic cells. Our data give evidence that different immune mechanisms are involved in the pathogenesis of INS.