Characterization of a 30,000-35,000 m.w. monokine involved in the specific immune response: intracellular production, secretion and partial purification.

Peritoneal macrophages from normal mice which do not secrete interleukin 1 (IL 1) spontaneously release a factor with an approximate m.w. of 30,000-35,000. In contrast, in the presence of silica only IL 1 is produced. IL 1 as well as this macrophage-replacing factor (MRF) can restore the antibody response of macrophage-depleted spleen cells. IL 1, however, is the only one that has the capacity to increase the proliferation of thymocytes. In every strain of mice studied, including nude mice, we observed a spontaneous release of MRF and a silica-induced shift to the secretion of IL 1, except in lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice. Macrophages from these mice are unable to secrete MRF spontaneously, or IL 1 when stimulated with silica. The kinetics of the secretion of MRF and IL 1 appear to be similar. Macrophages, regardless of whether they have been stimulated to secrete IL 1, produce an intracellular IL 1-like activity with an approximate m.w. of 15,000. In contrast, the intracellular PFC-restoring activity is widely distributed in the 15,000-60,000 m.w. range; one of these compounds could be related to IL 1 precursor and/or to MRF itself. Chromatofocusing and chromatography on Blue Trisacryl have led to a partial purification and resolution from a possible contamination by IL 1. Purified MRF induces, in conjunction with lymphokines, the differentiation of B cells into antibody-forming cells.