Interleukin 4 downregulates cell growth and prostaglandin release of human mesangial cells

Several clinical studies have proposed that a T cell derived cytokine IL-4 is operative in glomerulonephritis; however, its biological activities on renal cells have not been investigated. To elucidate its possible role in glomerulonephritis, we have examined whether IL-4 has effect on cell growth and prostaglandins synthesis using cultured mesangial cells (MC). IL-4 dose-dependently suppressed DNA synthesis and cell proliferation. IL-4 (10 ng/ml) alone did not affect prostaglandin E₂ (PGE₂) synthesis by mesangial cells, though, it inhibited IL-1α- and TNFα-stimulated PGE₂ synthesis by 48% and 81%, respectively. Comparable inhibition was observed on the conversion of exogenous arachidonic acid to PGs by IL-1-stimulated cells, suggesting IL-4 down regulates PG endoperoxide synthase activity. These results demonstrated that IL-4 is antagonistic to inflammatory cytokines upon PG synthesis as well as anti-mitogenic with MC.