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


CONCLUSIONS
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.
Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Japan.
M
M
Sakurai
E
E
Muso
H
H
Matushima
T
T
Ono
S
S
Sasayama
D001781:Blood Component Removal; D018932:Chemokine CCL2 / Q000097:blood; D004351:Drug Resistance; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000628:therapy; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000628:therapy; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood / Q000473:pathology / Q000628:therapy*; D013256:Steroids / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018932:Chemokine CCL2; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha