title: Glomerular ICAM-1 expression related to circulating TNF-alpha in human glomerulonephritis.
abstract: To clarify the in vivo involvement of cellular adhesion molecules and cytokines in human glomerulonephritis, we have investigated the glomerular and interstitial expression of intercellular adhesion molecule 1 (ICAM-1) in 69 kidney biopsy specimens by immunohistochemical methods and its correlation with serum bioactive tumor necrosis factor alpha (TNF-alpha) and soluble ICAM-1 (sICAM-1) levels in 43 cases. In normal controls, glomerular ICAM-1 expression and serum TNF-alpha and sICAM-1 levels showed a mean score of 1.0 (n = 7) and were 12.1 +/- 1.5 and 187 +/- 5 ng/ml (mean +/- SEM, n = 25), respectively. ICAM-1 was positive in 68 kidneys except in 1 patient with membranous nephropathy at various degrees in glomeruli and in 72% of peritubular capillaries or venules in the interstitium. Serum-bioactive TNF-alpha levels increased in the patients with IgA nephropathy, purpura nephritis, and lupus nephritis (LN) (18.9 +/- 4.1, 32.6 +/- 13.3, and 20.9 +/- 3.5 pg/ml) and were positively correlated with the grade of glomerular ICAM-1 expression (n = 43, r = 0.57, p < 0.001), endocapillary proliferation with exudative lesions (r = 0.72, p < 0.001) and hematuria (r = 0.62, p < 0.001). Serum sICAM-1 levels were elevated in patients with LN and purpura nephritis and decreased from 312 +/- 40 to 226 +/- 21 ng/ml after methylprednisolone pulse therapy in LN (n = 9, p = 0.0285). sICAM-1 levels were positively correlated with the grade of interstitial ICAM-1 expression (r = 0.46, p < 0.05), and sICAM-1 levels (>210 ng/ml) showed high odds ratios in the interstitial ICAM-1-positive cases and systemic vasculitides such as purpura nephritis and LN (6.00, p = 0.0355; 6.50, p = 0.0216, respectively). These results suggest that bioactive TNF-alpha might relate to glomerular ICAM-1 expression associated with endocapillary lesions in human glomerulonephritis and that sICAM-1 levels may be used as a clinical marker to assess interstitial lesions in human nephritis and systemic vasculitides.
authors.affiliation: 1st Department of Internal Medicine, Kanazawa University School of Medicine, Ishikawa, Japan. dialysis@med.kanazawa-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: M
authors.initials: M
authors.lastname: Takaeda
authors.forename: T
authors.initials: T
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: Y
authors.initials: Y
authors.lastname: Hisada
authors.forename: C
authors.initials: C
authors.lastname: Segawa
authors.forename: K
authors.initials: K
authors.lastname: Furuichi
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019867:Anti-Glomerular Basement Membrane Disease / Q000378:metabolism / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002648:Child; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D006417:Hematuria / Q000473:pathology / Q000652:urine; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D016482:Urinalysis; D014657:Vasculitis / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D008775:Methylprednisolone