Growing evidence suggests that cytokine expression is influenced by locally produced mediators, thus modifying the pluripotential effects of cytokines toward a tissue-specific inflammatory reaction. The granulocyte inhibitory protein (GIP), a 23-kDa protein found to be significantly overexpressed in patients with chronic renal failure, increases autocrine transcription and expression of interleukin (IL) 6 and IL-8 in human mesangial cells. Moreover, GIP alone induced the transcription of c-jun mRNA; however, in combination with IL-6, it stimulated de novo synthesis of DNA and the transcription of both c-jun and c-fos genes. The data suggest that the overall effect of GIP results in the modulation of the glomerular response to injury and contributes to the progression of glomerulosclerosis.