Interleukin 1, a potential regulator of fibroblast proliferation.

Abstract

Secondary mixed lymphocyte reaction (MLR) supernatants contain factors that stimulate fibroblast proliferation in vitro. Biochemical analysis of secondary MLR supernatants using gel filtration chromatography and isoelectrofocusing (IEF) demonstrated that the fibroblast proliferation factors have apparent m.w. of 75,000 and 13,000 and isoelectric points (pi) of 6.8 to 7.2, 5.8 to 6.2, and 5.2 to 5.4, values similar to those previously reported for human interleukin 1 (IL 1). To further explore the relationship between the MLR-derived fibroblast proliferation factors and IL 1, the following experiments were performed. First, the fractions obtained from gel filtration and IEF were assayed for both thymocyte proliferation activity, a measure of IL 1 activity, and fibroblast proliferation activity, and superimposable activity profiles were obtained. Second, to confirm that the observed thymocyte proliferation activity was in fact due to IL 1 and not interleukin 2 (IL 2) or novel factors, the IEF fractions containing peak thymocyte and fibroblast proliferation activity (i.e., fractions having pi of 6.8, 6.0, and 5.3, respectively) were demonstrated to stimulate IL 2 production by a murine T lymphoma line, a specific measure of IL 1 activity. Third, IL 1 and the fibroblast proliferation factors were co-purified through a three-step, 200-plus-fold purification protocol consisting of ammonium sulfate precipitation, gel filtration chromatography, and IEF. Fourth, partially purified human IL 1 made in another laboratory and highly purified murine IL 1, but not human and murine IL 2, stimulated fibroblast proliferation. These results demonstrate that the fibroblast proliferation factors found in secondary MLR supernatants have several functional and biochemical properties in common with human IL 1. These findings raise the possibility that IL 1 may regulate fibroblast proliferation and that the local production of IL 1 by infiltrating mononuclear cells may contribute to the fibrosis observed in chronic inflammatory disease states.