Purified murine colony-stimulating factors (CSF) recombinant interleukin 3 (IL-3), natural CSF-1, and recombinant granulocyte-macrophage (GM) CSF were assessed in vivo for their ef-

The capacity of a host to produce and mobilize monocytes is an essential component of host defenses during the early phases of infection caused by Listeria monocytogenes. In this study, the concentrations of colony stimulating factor (CSF) and the numbers of monocyte progenitor cells (CFUm) were measured in mice during infection with L. monocytogenes. The concentration of CSF in serum increased sharply during the first 24 h of infection and remained elevated for the next 7 days. The number of CFUm in the bone marrow, however, decreased during the first 4 days after injection of L. monocytogenes. Thereafter, the number increased slowly, returning to normal on day 14. The decrease in marrow progenitor cells did not appear to result from a reduced sensitivity to CSF. In contrast to bone marrow changes, spleen progenitor cells increased >400%, reaching a peak 7 days after bacterial challenge. These data indicate that monocyte production during L. monocytogenes infection is correlated with a rise in serum CSF concentration, depletion of bone marrow CFUm, and an increase in the number of spleen CFUm.

Studies were performed to determine changes in serum macrophage colony-stimulating factor (M-CSF) levels and the number of macrophage progenitor cells in bone marrow and spleens of nonimmune and immune mice infected with Listeria monocytogenes. Immunity in mice was established by infecting mice 6 weeks before use with a sublethal dose of L. monocytogenes. When challenged with 104 L. monocytogenes organisms, immune mice had an early (12 h) peak in M-CSF serum concentrations. Levels remained elevated for 24 h but fell towards normal by 48 h. By contrast, M-CSF levels in nonimmune mice did not rise until 24 h after challenge, remained elevated for 7 days, and returned to normal by 14 days. The number of macrophage progenitor cells in the bone marrow of immune mice rose slightly during infection, whereas the number in nonimmune mice fell significantly by days 4 and 7. Progenitor cells in spleens of immune mice more than doubled during infection; in nonimmune mice, a sixfold increase was noted. These results indicate that important parameters of monocyte production differ in immune and nonimmune mice during listeria infection and suggest a possible mechanism for differences in resistance to infection.

The effects of L-cell conditioned medium which contains granulocyte/macrophage colony stimulating factor (CSF); of highly purified L-cell CSF; and the antiserum directed against L-cell CSF, have been investigated in long-term murine bone marrow cultures. Treatment of cultures with CSF containing conditioned medium led to a rapid decline in haemopoiesis. However, this inhibition of in vitro haemopoiesis is probably caused by materials other than CSF, since the addition of highly purified L-cell CSF had no appreciable effect upon long-term haemopoietic cell proliferation or differentiation. Furthermore, the inhibitory activity of L-cell conditioned medium was not abrogated following neutralization of the CSF activity by CSF antiserum. The direct addition of CSF antiserum did not inhibit granulocyte or macrophage formation. These results suggest that long-term cultures of murine marrow cells may show extensive interactions with stromal cells which are not influenced by exogenous stimulatory or inhibitory factors.