Effect of leukocyte stimulation on rabbit immune complex glomerulonephritis.

Phytohemagglutinin (PHA), a leukocyte mitogen, induces a lymphocyte and blast cell glomerulonephritis in rat renal allografts (Cell Immunol 13:146, 1974). The aim of this study was to assess whether PHA similarly enhances rabbit monocyte-dependent experimental, acute immune complex glomerulonephritis, and whether this effect is associated with local release of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Rabbits with experimental acute serum sickness (AcSS: Group I) had focal proliferative and exudative glomerulonephritis with immune deposits, scattered subepithelial electron-dense deposits (humps), mild and transient proteinuria, normal creatinine clearance and slightly increased production of IL-1 and TNF from isolated glomeruli. Rabbits with AcSS and injected with PHA (Group II) developed severe lymphocyte and blast cell glomerulonephritis with diffuse endothelial damage; immune deposits were significantly reduced, focal subepithelial electron-dense deposits were absent, proteinuria was increased, creatinine clearance was decreased and production of IL-1 and TNF was markedly augmented as compared to rabbits in Group I. Rabbits with AcSS and injected with IL-1 beta and TNF alpha (Group V) had lesions comparable to those seen in Group II. These results show that PHA, IL-1 and TNF enhance the severity of acute immune complex glomerulonephritis, presumably by activating glomerular endothelial and mesangial cells and resident or infiltrated leukocytes.