It is well known that macrophages of the reticuloendothelial system take up antigens before the initiation of the immune response (1) and that injections of bacterial endotoxins first depress and then stimulate the phagocytic activity of these cells (2, 3). In view of these facts, a study has been made of the influence of a Salmonella typhosa endotoxin on the production of specific immunoglobulins, in the hope of learning something more about the role of phagocytic cells in the process of antibody formation. A particulate antigen, the sheep red blood cell, was employed in this investigation so that changes in the uptake and processing of antigen might more readily be reflected as differences in the resulting formation of antibodies. When the endotoxin was given simultaneously with this antigen, the adjuvant effect on antibody formation previously described by others using soluble antigens (4, 5) was promptly confirmed.On the other hand when the bacterial preparation was allowed to exert a more sustaining action and was given prior to the particulate antigen, it was found to suppress instead of enhance the production of hemolysins. This surprising effect, which in many instances resulted in the complete inhibition of antibody production, was realized by employing appropriate time intervals between the injection of endotoxin and the particulate antigen, and suitable routes of administration of these agents. These results are detailed in the present paper together with other serological findings on the effects of endotoxin on hemolysin production in mice. Subsequent to a preliminary communication of these findings (6), others (7,8) have also reported that, under specified conditions, bacterial endotoxins will inhibit the production of antibodies to particulate antigens.The pronounced inhibition and enhancement of antibody formation, which could be brought about at will by the proper use of endotoxin, offered an excellent opportunity to investigate the cellular changes in the antibody-forming
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