Tumor necrosis factor in renal injury.
Inflammatory diseases of the renal glomerulus and tubulointerstitium are characterized by destructive and restorative processes. These alterations are mediated by soluble molecules, including cytokines that instruct target cells to alter their proliferation, differentiation phenotype, secretion and migration. One of these cytokines is tumor necrosis factor-alpha (TNF alpha). Its expression within the glomerulus has been observed in both resident cells and infiltrating monocytes/macrophages in response to cell stimulation with chemicals, immune complexes, bacterial lipopolysaccharides, and advanced glycosylation end products. Its release can be amplified by deposits of terminal complement proteins (C5b-9) or formation of platelet-activating factor and reactive oxygen species, and, on the contrary, blunted by that of prostaglandins or anti-inflammatory interleukin (IL)-6 and IL-10. The roles of TNF alpha in the pathogenesis of glomerular diseases include reduction of blood flow and filtration rate, alteration of the barrier function of capillary wall, formation of capillary thrombi and infiltration of the structure by blood-borne cells. Expression of TNF alpha has been observed in tubulointerstitium as well, mainly in proximal tubular epithelial cells. In vitro, this expression can be amplified by IL-1 and, inversely, suppressed by immunosuppressive drugs. Roles of TNF alpha in tubulointerstitium remain largely undefined, but may include infiltration of the interstitium by inflammatory cells and alteration in tubular transport of fluid and electrolytes. Extensive study will be necessary to further elucidate intracellular signals induced by TNF alpha binding to target cells within the kidney and thus to establish possibilities of therapeutic intervention.
Baud
L
L
INSERM U.64, Hôpital Tenon, Paris, France.
Ardaillou
R
R
D000818:Animals; D005921:Glomerulonephritis / Q000209:etiology*; D006801:Humans; D009395:Nephritis, Interstitial / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha