Cytokines and adhesion molecules in renal vasculitis and lupus nephritis.
BACKGROUND
Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules.


METHODS
Plasma levels and urinary excretion of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 14 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated.


RESULTS
Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-alpha (9.27 +/- 3.19% vs 0.58 +/- 0.02%, P < 0.01), IL-6 (120.79 +/- 65.83% vs 1.89 +/- 0.34%, P < 0.01) and increased fractional excretion of IL-8 (23.34 +/- 6.38% vs 2.56 +/- 1.07%, P < 0.01) and sVCAM-1 (0.81 +/- 0.33% vs 0.03 +/- 0.02%, P < 0.01) compared with controls. Urinary excretion of TNF-alpha and IL-6 and fractional excretion of TNFalpha, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-alpha (20.52 +/- 2.01 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05) and sVCAM-1 (1537.88 +/- 276.36 ng/ml vs 692.26 +/- 44.42 ng/ml, P < 0.05) and increased urinary excretion of TNF-alpha (2.81 +/- 0.51 microg/mol creat vs 0.98 +/- 0.05 microg/mol creat, P < 0.01), IL-8 (35.78 +/- 14.03 microg/mol creat vs 12.46 +/- 5.19 microg/mol creat, P < 0.05) and sVCAM-1 (48.98 +/- 20.20 microg/mol creat vs 2.92 +/- 1.35 microg/mol creat, P < 0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-alpha (18.10 +/- 0.57 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05).


CONCLUSIONS
Urinary excretion and fractional excretion, but not plasma levels, of selected pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.
Tesar
V
V
1st Department of Medicine, Charles University, Prague, Czechoslovakia.
Masek
Z
Z
Rychlík
I
I
Merta
M
M
Bartůnková
J
J
Stejskalová
A
A
Zabka
J
J
Janatková
I
I
Fuciková
T
T
Dostál
C
C
Becvár
R
R
D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood / Q000652:urine*; D016207:Cytokines / Q000097:blood / Q000652:urine*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000652:urine; D015850:Interleukin-6 / Q000097:blood / Q000652:urine; D016209:Interleukin-8 / Q000097:blood / Q000652:urine; D007674:Kidney Diseases / Q000188:drug therapy / Q000276:immunology*; D008181:Lupus Nephritis / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000652:urine; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000652:urine; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1