To investigate the possible role of
cytokines in the mediation of glomerular injury in the
nephrotic syndrome, the levels of
interleukin (IL)-1 beta,
IL-2,
interferon (IFN)-alpha, IFN-gamma, and
tumor necrosis factor-alpha (
TNF-alpha) were measured in patients with primary
nephrotic syndrome. These patients had
minimal change nephropathy (MCN), focal and
segmental glomerulosclerosis (FSGS), or
membranous nephropathy (MN) on biopsy.
Cytokine levels were assessed by immunoradiometric assays, and specimens consisted of plasma, urine, and the culture supernate of
mitogen-stimulated peripheral blood mononuclear cells (PBMC). Only
TNF-alpha was found to be significantly elevated, in the plasma and urine of patients with FSGS and MN, above that found in healthy control subjects and patients with MCN. The elevation of
TNF-alpha could not be shown to correlate with the length or severity of the
nephrotic syndrome or with loss of body mass.
IL-1 beta,
IL-2, IFN-alpha, and IFN-gamma levels were not elevated. In culture,
mitogen-stimulated PBMC from all three groups of nephrotic subjects released an excess of
TNF-alpha compared with controls, a response not consistently observed for the other
cytokines measured. The findings of this survey of
cytokine levels in nephrotic patients support the possibility that
TNF-alpha may play a pathogenic role in the induction or maintenance of glomerular barrier dysfunction in humans.