Effect of interleukin 1, macrophage colony-stimulating factor, and factor increasing monocytopoiesis on the production of leukocytes in mice.

The present study was designed to establish that the factor increasing monocytopoiesis (FIM) is a unique factor that differs from interleukin 1 (IL-1) and macrophage colony-stimulating factor (M-CSF) in its effect on the production of granulocytes, lymphocytes, and monocytes in C3H/HeJ mice, which are unresponsive to lipopolysaccharide. [3H]thymidine, together with the cytokine under study, was used as a marker for newly formed cells. The number of each category of labeled leukocytes in the circulation was calculated from the number of leukocytes per microliter of blood, differential counts of the leukocytes, and their labeling indices, as determined by autoradiography. To compare the effect of the various cytokines on the production of leukocytes, the area under the curve (AUC) of the number of each category of leukocytes over a period of 96 h has been calculated. The results show that IL-1 causes, within 2 h, an increase in the number of circulating granulocytes, most probably by recruitment of these cells from the storage pool in the bone marrow and the marginating pool in the blood vessels. This is followed by an increased production of granulocytes; the production of monocytes and lymphocytes is not affected by IL-1. Administration of M-CSF had no significant effect on the production of granulocytes, lymphocytes, or monocytes in vivo. FIM specifically stimulated the production of monocytes and had no effect on the other cell lineages. Because FIM is synthesized and secreted by macrophages upon phagocytosis at the site of an inflammation, this study indicates that FIM is a monokine that acts as a long-range regulator to signal the bone marrow to increase monocyte production during an acute demand for more monocytes and (exudate) macrophages.