T-LYMPHOCYTE POPULATIONS, CYTOKINES AND OTHER GROWTH-FACTORS IN SERUMAND URINE OF CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME

The T-cell defect present in the idiopathic nephrotic syndrome (INS) w as investigated in 29 steroid-sensitive and 14 steroid-resistant child ren aged 2-19 years. Nine different lymphocyte subpopulations and 15 c ytokines, receptors and other growth factors were measured in blood, a nd some also in urine. In steroid-sensitive patients we found a decrea sed ratio of helper/inducer cells (CD4+) versus suppressor/cytotoxic c ells (CD8+) in relapse and remission, and an increased proportion of n atural killer cells (CD16+) during relapse vs long-term remission, as a sign of an elevated cytotoxic potential. Among the serum cytokines m ainly produced by monocytes/macrophages interleukin (IL)-8 levels were decreased in steroid-sensitive patients vs controls, with normal leve ls observed for IL-1 alpha, IL-1 beta, IL-1RA and tumor necrosis facto r (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 slL-2R and IFN-gamma. Ser um levels of cytokines derived from TH2 cells were variable. IL-4 was decreased during relapse but increased in patients with long-term remi ssion. SIL-6 receptors were increased during relapse. Finally we obser ved 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 patie nts; their CD4+/CD8+ ratio was reduced to the same degree and sIL-2R l evels were even higher than in steroid-sensitive patients. In conclusi on this study indicates that active INS is associated with an increase d 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.