mo CHEMOTHERAPY OF BACTERIAL DISEASES 



words, the toxins of the disease or some other agencies may have a detoxifying efifect 

 upon the drug administered, 



INFLUENCE OF IMMUNOLOGICAL FACTORS 



Until we succeed in producing far more satisfactory chemotherapeutic compounds 

 for the treatment of bacterial diseases than available at present, recovery will con- 

 tinue to depend largely upon immunological processes aided in some diseases by 

 biological therapy (vaccines, sera, blood transfusion, etc.). The question naturally 

 arises whether or not it is possible for us to aid immunological processes by the ad- 

 ministration of drugs. To be classed in the domain of chemotherapy, must drugs 

 increase antibody production or aid and facilitate phagocytosis in bacterial diseases? 



We hear and read a great deal about arsphenamin and its congeners increasing 

 antibody production or aiding immunological processes in syphilis and trypanoso- 

 miasis, but the evidence presented so far is not very convincing. In bacterial diseases, 

 however, acquired immunity is developed to a greater degree and plays a far more 

 important part in recovery than in syphilis, and anything that may be safely done to 

 hasten or increase these beneficial changes is to be welcomed. 



In the first place, the intravenous administration of mercurochrome, other heavy 

 metals, and some of the dyes, quinin compounds, etc., commonly employed at present 

 in bacterial chemotherapy, may increase the leukocytes of the blood and especially 

 the polymorphonuclear neutrophils which we regard as playing a very important 

 part in natural and acquired resistance and immunity. The doses required, however, 

 for this result are usually the maximum amounts by intravenous injection. Unques- 

 tionably it is reasonable to expect that these leukocytes will prove of aid in overcom- 

 ing the infection, and the clinical reaction following the intravenous injection of 

 mercurochrome and other heavy metals bears such a close resemblance to the so- 

 called "non-specific protein" reactions produced by the intravenous injection of pep- 

 tone, vaccines, etc., that one cannot escape the suspicion that a good part of the 

 curative results may be due to the same mechanism as is called into play by the ad- 

 ministration of these protein agents. 



But I have had so far no clear or conclusive evidence of the increased production 

 of such humoral antibodies as the antitoxins, agglutinins, precipitins, opsonins, and 

 bacteriolysins during the course of experimental or natural bacterial infections, to be 

 ascribed to the influence of such drugs as optochin, gentian violet, acriflavin, and 

 mercurochrome. It may be that such compounds actually stimulate the production of 

 antibodies, since the production of leukocytosis indicates that the bone marrow and 

 the antibody-producing tissues in general may be stimulated, but it is difficult or im- 

 possible with present test tube methods to elicit and present the evidence. It is true 

 that the administration of these compounds to normal animals may increase tempo- 

 rarily their resistance to bacterial infection in a manner analogous to the temporary 

 resistance of mice and rats, treated with some of the dyes, to inoculation with patho- 

 genic trypanosomes ; but the resistance is of such short duration that one cannot be 

 sure that the results are not due rather to a retention of some of the compound in the 

 blood and tissues than to an increase of immunological resistance. But it may be that 

 some of our chemotherapeutic compounds may actually aid in immunological re- 



