Rapid normalization of interleukin-8 production after low-density lipoprotein apheresis in steroid-resistant nephrotic syndrome.

Abstract

BACKGROUND:

Low-density lipoprotein apheresis (LDL-A) treatment combined with steroids demonstrated significant improvement of nephrotic proteinuria in steroid- or immunosuppressive-resistant patients from focal and segmental glomerulosclerosis (FGS). The mechanisms of the effect of LDL-A in nephrotic syndrome (NS) are unknown, but a reduction in inflammatory cytokines and chemokines secreted from macrophages has been supposed.

METHODS:

Serum levels of interleukin (IL)-8, tumor necrosis factor-alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay in 27 patients with NS [13 with FGS and 14 with minimal change nephrotic syndrome (MCNS)] before and after LDL-A and in 13 age-matched, healthy controls. We also selected three FGS patients who were resistant to steroid therapy for at least one month and who had undergone six LDL-A procedures. The effects of steroids and LDL-A on the production of IL-8, TNF-alpha, and MCP-1 by peripheral blood mononuclear cells (PBMCs) were also determined in some patients.

RESULTS:

In NS, the serum levels of IL-8 and TNF-alpha, but not MCP-1, were significantly higher than in healthy controls. After LDL-A, IL-8 and TNF-alpha tended to decrease. IL-8 production by lipopolysaccharide (LPS)-stimulated PBMC, mainly adherent cells, was significantly reduced in both the steroid-resistant FGS group and nontreated NS group compared with controls, but TNF-alpha production was reduced in the only FGS group. After LDL-A, only IL-8 production recovered to the control group level.

CONCLUSION:

Significant amelioration of IL-8 production independent of any effect of steroids on LPS-stimulated PBMCs may reflect a beneficial effect of LDL-A in normalizing the function of circulating monocytes in steroid-resistant FGS.

• Authors: M Sakurai, E Muso, H Matushima, T Ono, S Sasayama
• Journal: Kidney international. Supplement (Kidney Int Suppl) Vol. 71 Pg. S210-2 (Jul 1999) ISSN: 0098-6577 [Print] United States
• PMID: 10412778 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article)

Chemical References

• Chemokine CCL2
• Interleukin-8
• Lipoproteins, LDL
• Steroids
• Tumor Necrosis Factor-alpha

Topics

• Blood Component Removal
• Chemokine CCL2 (blood)
• Drug Resistance
• Female
• Glomerulonephritis, Membranous (blood, therapy)
• Glomerulosclerosis, Focal Segmental (blood, therapy)
• Humans
• Interleukin-8 (blood)
• Leukocytes, Mononuclear (cytology, drug effects, metabolism)
• Lipoproteins, LDL (blood)
• Male
• Nephrotic Syndrome (blood, pathology, therapy)
• Steroids (therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)