Because of its interference with the formation of messenger ribonucleic acid, actinomycin D has come to be regarded as a general inhibitor of protein synthesis. Under certain conditions, however, the drug has the opposite net effect and appears to enhance protein synthesis. This paradoxical phenomenon has been examined in bacteria, rats, and many different mammalian culture systems (see DISCUSSION). The proteins most frequently studied have been various induced enzymes. One postulated explanation of this phenomenon is that synthesis of the induced enzyme is modulated by an inhibitor normally appearing soon after enzyme induction and that under certain conditions inhibitor formation may be selectively suppressed by acfinomycin. Clearly, isolation of the postulated inhibitor would provide the most convincing evidence for this hypothesis.

Under certain conditions the immune response also may be enhanced by actinomycin. This paper describes both the inhibitory and enhancing effects of the drug on the secondary antibody response in rabbit lymph node cultures. The conditions found critical for enhancement in vitro, such as the timing and level of actinomycin D treatment, are also those theoretically essential for the hypothesis described above. However, greater support for the hypothesis comes from our recovery in used culture medium of a nondialyzable inhibitor of antibody synthesis. Various features of this macromolecule suggest that it is the postulated inhibitor. These studies thus imply a control mechanism for antibody synthesis not widely suspected by immunologists.