Cortisone on Tissue Cultures

NUMEROUS recent reports show that cortisone apparently exerts an inhibitory effect, both clinically and in experimental animals, on mesenchymal growth; the evidence on its effect upon epithelial cells is less conclusive. This work has been reviewed by Duke-Elder and Ashton (1951). The object of the experiments here reported is to elucidate the action of cortisone on growth in tissue cultures and to ascertain whether any effect it may have is direct or indirect in its action. Little work on this aspect has been published. The effect of cortisone upon epidermal cells of the mouse has been studied by Green and Ghadially (1951); they found that cortisone was a powerful inhibitor of mitosis in the pre-prophase stage. Cornman (1951) states that desoxycorticosterone acetate (DOCA) and cortisone acetate selectively damage fibroblasts without in any way affecting epithelial growth. These results, however, were obtained by replacing the fluid phase of the cultures by a solution of DOCA in saline, an apparently nonnutrient medium. Furthermore, he found that if 10 per cent. of the saline were replaced by serum no such effect on the tissue cultures was seen up to concentrations of 0.03 mg./ml. DOCA or up to 0.026 mg./ml. cortisone acetate. This suggests that unless the conditions are quite artificial, cortisone acetate does not, in fact, suppress the growth of the cells. Barber and Delaunay (1951) injected guinea-pigs with large doses of cortisone, and found that plasma from these animals inhibited the growth of fibroblasts in tissue culture. Their experimental results cannot be regarded as conclusive, however, for only eleven of twenty specimens of plasma showed this effect and the large doses of cortisone produced severe constitutional disturbances in the animals, some even dying before the blood could be taken. Holden and others (1951) studied the effect of cortisone on tissue cultures of spleens from mice, guinea-pigs, and rabbits. The highest concentrations of cortisone they used (which were only 1/100th of the lowest concentration used in our experiments) produced moderate or marked inhibition of fibroblastic growth, whereas their lower concentrations had no such effect. It is obvious that further work on this question is desirable.