Growth-stimulating phase of macrophage response to activation: the phenomenon and its implications for tumour growth and immunotherapy.

The dynamics of growth-stimulating and cytotoxic activity of mouse peritoneal macrophages (PMo) in response to in vivo and in vitro bacillus Calmette-Guérin (BCG) or bestatin treatment was studied. It was shown that BCG and bestatin induce cytotoxicity in PMo, and that after the cytotoxic response strong growth-stimulating activity develops. PMo, rendered cytotoxic in vivo and afterwards cultivated in vitro, displayed the same switch from a cytotoxic to a growth-stimulating phase. These results suggest that the growth-stimulating phase is the obligatory PMo response to biological response modifiers (BRM) at least to BCG and bestatin. The growth rate of tumours, transplanted into mice during the cytotoxic phase of the response to BCG, was suppressed, whereas tumours transplanted during the growth-stimulating phase were stimulated. It appears that the development of a growth-stimulating phase after the cytotoxic phase of response to activation by BRM could be one of the reasons for the limited effectiveness of immunotherapy based on the application of macrophage activators.