title: Interleukin-15 and interleukin-12 have an additive effect on the release of vascular permeability factor by peripheral blood mononuclear cells in normals and in patients with nephrotic syndrome.
abstract: BACKGROUND
  The vascular permeability factor (VPF) is a lymphokine that has been shown to play a role in minimal-change nephrotic syndrome (MCNS). A better understanding of the mechanisms that upregulate VPF release is of basic importance to control the immune system in nephrotic syndrome (NS). Interleukin (IL)-15 is a key inducer of differentiation of uncommitted T helper cells, which regulates cellular immunity. The cytokine IL-15 appears to mimic the stimulatory activity of IL-2 on T cells.
  
  
  METHODS
  In the present report, we studied the ability of IL-15, alone or in combination with IL-12, to influence the release of VPF by peripheral blood mononuclear cells (PBMC) from nephrotic patients. We have analyzed the release of VPF by concanavalin-A- (Con A) stimulated PBMC in normals, 16 patients with MCNS and 16 patients with IgA nephropathy (IgAN).
  
  
  RESULTS
  In both patient groups 50% had a proteinuria below 0.8 g/day. We demonstrate that nephrotic, but not non-nephrotic patients (both MCNS and IgAN), exhibit a high VPF release, which can be stimulated further by IL-15 + IL-12. To determine the specificity of the stimulatory effect, neutralizing anti-IL-15 and anti-IL-12 antibodies were preincubated with IL- 15 and IL-12 prior to the addition of responder cells, respectively. The antibodies completely inhibited the effects of IL-15 and IL-12.
  
  
  CONCLUSIONS
  These results indicate that IL-15 plus IL-12 acted additively to augment VPF release. These biological interactions between IL-15 and IL-12 may be important in the pathophysiology of VPF in vitro.
authors.affiliation: Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Kanmatsuse
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004357:Drug Synergism; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D019409:Interleukin-15 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D009402:Nephrosis, Lipoid / Q000188:drug therapy / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000378:metabolism*; D011239:Prednisolone / Q000627:therapeutic use; D020033:Protein Isoforms / Q000378:metabolism; D012016:Reference Values; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D019409:Interleukin-15; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003208:Concanavalin A; D018664:Interleukin-12; D011239:Prednisolone