[Production and proinflammatory activity of tumor necrosis factor alpha in the glomerulus]

The production and the effects of tumor necrosis factor alpha (TNF alpha) have been studied in isolated glomeruli and cultured glomerular cells from animal or human origin. Glomeruli from rats injected with E. coli lipopolysaccharide (LPS) and glomeruli exposed to LPS in vitro release TNF alpha into the medium. The glomerular cells responsible for TNF alpha synthesis are mesangial cells. Production of TNF alpha is controlled by other locally produced mediators. Prostaglandin E2 and interleukin-10 are inhibitory. Hydroxyl radicals stimulate the transformation of the transmembrane form of TNF alpha into its soluble form which is secreted into the medium. TNF alpha acts on its producing cells and on the neighbouring cells. It induces contraction of mesangial cells, increases the synthesis of a variety of local mediators including prostaglandins, platelet-activating factor and chemotactic agents, particularly interleukin-8. Synthesis of this cytokine implies activation of tyrosine kinase and of transcription factors, essentially NFkB. Taken together, these results suggest that TNF alpha plays a marked role in the development of glomerular injury and incite us to search for treatments inhibiting its synthesis and its effects.