Interferon‐gamma stimulates the secretion of IL‐1, but not of IL‐6, by glomerular mesangial cells

SUMMARY IL‐1 activity in culture supernatant and cell lysate from rat mesangial cells stimulated with interferon‐gamma (IFN‐γ) was measured by a thymocytc proliferation assay. While IFN‐γ alone had no effect on the secretion or the intracellular pool of IL‐1, the enhancement by IFN‐γ of IL‐1 secretion in response to lipopolysaccharide (LPS) was observed. The stimulatory effect of culture supernatant on thymocyte proliferation was abrogated by preincubation with the anti‐IL‐l antibody. At least 4–h incubation with IFN‐γ and LPS was required to detect enhancing effect of I FN‐γ. The addition of as little as 1 U/ml IFN‐γ significantly increased IL‐1 secretion in the presence of 10 μg/ml LPS. The IL‐6 activity in culture supernatants was determined by measurement of thymidine uptake in mouse IL‐6‐dependent cell line (MH60.BSF2). Mesangial cells secreted IL‐6 in culture supernatant without additional stimuli and LPS distinctly increased it as described previously. However, in contrast to IL‐1 production, no effect of IFN‐γ on IL‐6 secretion was observed in the presence or absence of LPS. Moreover, we determined whether enhanced IL‐1 release is associated with la expression on mesangial cells. IFN‐γ alone and the combination with LPS induced marked expression of la antigen, whereas LPS alone did not. We conclude that IFN‐γ stimulates the production of IL‐1, but not IL‐6, by mesangial cells and suggest an important role of IFN‐γ in the pathogenesis of glomerulonephritis by regulating the mesangial production of IL‐1 and the accessory cell function of mesangial cells.