SELECTIVE INDUCTION OF PDGF GENE-EXPRESSION IN PERITONEAL-MACROPHAGESBY INTERLEUKIN-2

We have previously reported that culture of human peripheral blood leu kocytes with interleukin-2 (IL-2) triggers the secretion of mediators which induce fibroblast proliferation and collagen synthesis. In addit ion, fibrogenic cytokines (transforming growth factor-beta B-1 (TGF be ta(1)) and platelet-derived growth factor (PDGF) A and B chain) are pr esent in the peritoneal fluid of patients undergoing intraperitoneal i mmunotherapy (IL-2-activated killer cells and IL-2) who go on to devel op peritoneal adhesions. To determine the role of IL-2 in the formatio n of these adhesions, we chose to investigate whether IL-2 can induce the expression of fibrogenic cytokine genes in resident rat peritoneal macrophages. Cells were cultured with or without IL-2 or lipopolysacc haride (LPS) and expression of PDGF A chain, PDGF B chain, and TGF bet a(1) mRNAs was determined. PDGF A and B chain mRNAs are minimally expr essed in macrophages prior to stimulation and are induced within 2 hou rs of treatment with IL-2. In contrast, TGF beta(1) mRNA is constituti vely expressed and can not be upregulated. The studies suggest that pe ritoneal macrophage-derived PDGF plays a critical role in the producti on of adhesions in patients receiving intra-abdominal immunotherapy.