Effect of mouse peritoneal macrophages of orally administered very high dilutions of silica

The activity of very high dilutions of silica, a substance cytotoxic for macrophages, was tested on the synthesis by mouse peritoneal macrophages of the inflammatory ether-lipid paf-acether and its precursor lyso paf-acether. C57Bl6 female mice received for 25 days either 1.66 X 10(-11) M silica (11 sil) or 1.66 X 10(-19) M (19 sil) (final concentration) in the tap-water they were given to drink while control mice remained untreated. Isolated macrophages from mice treated with 11 sil produced 44.2 and 30.8% more paf-acether than cells from untreated mice in the presence of 50 and 200 micrograms zymosan (Z)/ml respectively. When 19 sil was given to the mice, the respective increases were 67.5 and 38%. In an experiment with a blind design, the mice were either untreated or received 19 sil or saline submitted to the same dilution procedure (19 sal). After administration of 19 sil, paf-acether synthesis was 55.5 and 33.5% higher upon stimulation with 50 and 200 micrograms Z/ml, respectively, than in the 19 sal group. In a third blind experiment, macrophages from mice that received 19 sil formed 61.3 and 28.6% more paf-acether upon stimulation with 50 and 200 micrograms Z/ml respectively, as compared to mice receiving 19 sal or lactose submitted to the same dilution procedure (19 lac). There was no difference between the 19 sal and the 19 lac groups. The differences between control and silica-treated mice were highly statistically significant in all experiments. There was no effect on the synthesis of lyso paf-acether. These results demonstrate clear ex vivo cellular effect of high dilutions of silica, that cannot be explained in our present state of knowledge.