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.
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.
Matsumoto
K
K
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Kanmatsuse
K
K
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
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