Glomerular ICAM-1 expression related to circulating TNF-alpha in human glomerulonephritis

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.