Neutrophil involvement in effects of diethylstilbestrol and strontium 89 on macrophage activation by Propionibacterium acnes.

We have recently demonstrated that diethylstilbestrol (DES) significantly suppresses macrophage (M phi) activation by Propionibacterium acnes. Because the initial activation of M phi by P. acnes appears to involve the close interaction of the killed bacteria with inflammatory neutrophils (PMN) and resident M phi in the peritoneal cavity, we investigated whether the DES inhibition of M phi activation was associated with inhibition of the PMN response. Our data demonstrate that treatment of mice with DES did not interfere with the acute inflammatory peritoneal PMN influx 5 h after P. acnes injection. DES treatment also did not affect development of the early (day 4) tumor cytotoxic activity of P. acnes activated M phi; this M phi activity has been shown to be mediated by the acute PMN influx. DES treatment, however, did reduce M phi activation as evidenced by alterations in other markers typically associated with M phi activation by P. acnes, including the characteristic reductions in alkaline phosphodiesterase (APD) ectoenzyme activity and the total RNA synthesis, as well as the characteristic persistence of the peritoneal PMN response seen on days 4 and 7 after P. acnes injection. In addition, M phi activity 7 days after P. acnes injection was inhibited in DES treated mice, as evidenced by reduced antitumor activity, and alteration of the markers mentioned above. As a second approach to elucidate the involvement of the acute and persistent PMN response in the M phi activation process, we depleted mice of circulating PMN by treatment of mice with 89Sr before administration of P. acnes.(ABSTRACT TRUNCATED AT 250 WORDS)