Co-induction of lymphokine synthesis by the antineoplastic bryostatins

The macrocyclic lactone bryostatins, isolated from marine bryozoans, have been found to be strong inhibitors of e.g., the P 388 murine lymphocyte leukemia cell line and in vivo systems. Presently, bryostatin 1 is under preclinical development as a potential anticancer drug, although the bryostatins exhibit some of the same biological effects as the tumor promoting phorbol-12-myristate-13-acetate (PMA), especially activation of protein kinase C in certain cell types. In our experiments, we investigated the influence of bryostatin 1 on the synthesis of interleukin 2 (IL2) and interferon-gamma (IFN-gamma) by ionophore A23187 or mitogen-induced human blood lymphocytes. These results were then compared with those achieved using the two tumor promotors PMA and teleocidin. Our data indicate that bryostatin 1 is comparable to these two other drugs in increasing production of the two lymphokines 10-100-fold. The IL2 and IFN-gamma production kinetics of cultures induced with either A23187/bryostatin 1 or A23187/PMA were practically identical. The general pattern of peptides, however, released from bryostatin 1 coinduced cultures differed from that obtained when PMA was used.