We studied the determinants of maximum bile acid secretory rate (SRm) in the rat. The choledochocaval fistula rat model manifested a bile acid secretory rate far in excess of the SRm previously reported for taurocholate in this species. We studied the ability of various bile acid solutions to maintain the high secretion rate in this model. Whole-rat bile, but not taurocholate in 2% albumin nor rat bile with bile acid content over 90% taurocholate, maintained secretion rate. We concluded that the mixture of bile acids in rat bile was the most important determinant of the high secretion rate and that the high rate was not due to a peculiarity of the model itself nor to the infusion of biliary lipids together with bile acids. Conventional determination of the SRm in the bile fistula rat confirmed this impression, with the least toxic bile acids manifesting the highest SRm. During infusion of taurocholate beyond the SRm, bile flow and bile acid secretion rate fell. This was accompanied only by scattered focal necrosis of single liver cells or of small aggregates of cells and not by any diffuse subcellular morphological change. We believe the maximum bile acid secretory rate is determined by toxicity of a specific bile acid for the secretory mechanism rather than by a limitation in transport receptor number as is usual with substances manifesting classical transport maxima. The high SRm of the 7 beta-hydroxy bile acid, ursodeoxycholic acid, is probably related to its very low toxicity. The high SRm in the choledochocaval fistula rat is probably related to the presence of 7 beta-hydroxy muricholic acids in the bile of this species.

Stimulators of human erythroid burst-forming units (BFU-E) and multipotential colony-forming cells (CFU-GEMM) can be produced by a number of different cell types. A product of human peripheral blood monocytes, interleukin 1 (IL-1), was evaluated for its ability to stimulate fibroblast cultures to produce stimulators of human bone marrow BFU-E and CFU-GEMM colony formation. BFU-E and CFU-GEMM colony formation was evaluated using low-density, nonadherent low-density, and T lymphocyte-depleted nonadherent low-density human bone marrow cells cultured in the presence of a source of pure human erythropoietin. Both human monocyte conditioned medium (MCM) and human recombinant IL-1 (hrIL-1) induced fibroblasts to produce stimulators of BFU-E and CFU- GEMM in a dose-dependent fashion with maximal colony formation occurring when fibroblasts were stimulated by 25% MCM or 140 ng/mL ROO6B hrIL-1, or 1.25 to 5 ng/mL ROO6T hrIL-1. Preincubation of MCM and hrIL-1 with an antibody to IL-1 inactivated the ability of MCM and hrIL- 1 to induce the release of erythroid and multipotential colony stimulating activity from fibroblasts. These results suggest that monocyte-derived IL-1 is involved in regulating the production of humoral stimulators of early human hematopoietic progenitors.

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