Diminished response of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mice after sensitisation with bacterial cell-wall components.

The secondary induction of serum granulocyte-macrophage colony-stimulating factor (GM-CSF) by structurally unrelated and chemically highly purified bacterial cell-wall components (BCWC) was studied. Homologous challenge of mice 7 days after treatment with lipid A, lipoprotein or murein failed to increase serum GM-CSF levels and the extent of the decreased responsiveness was dependent upon the dose used for the initial injection. Lipid A-induced decreased responsiveness took 48 hours to develop and remained fully expressed approximately up to day 7 following injection. Then responsiveness reappeared gradually and was virtually normal 4 weeks after injection. Lipoprotein-induced decreased responsiveness developed in a similar manner but peristed maximally over the whole 8 week period studied. The decreased responsiveness induced by the injection, 7 days previously of either lipid A or lipoprotein was not specific as cross-challenge also failed to elevated GM-CSF to normal levels. On the other hand, 7 weeks after priming the lipoprotein induced decreased responsiveness was found to be specific. Mixing experiments failed to show increased levels of GM-CSF inhibitors in the serum from mice injected 7 days previously with lipid A and decreased responsiveness could not be transferred with serum to normal recipients. Similarly the lowered GM-CSF response to lipoprotein could not be transferred wth serum collected 7 weeks after primary injection. Medium conditioned by spleens from mice injected with lipid A contained less detectable GM-CSF than medium conditioned by normal spleens, but a variety of other organs did not show this difference. Mixing experiments failed to show significant differences in GM-CSF inhibitory activity between the two types of spleen conditioned media.