THE ORGANOTROPIC, BACTERIOTROPIC, AND LEUCOCYTOTROPIC ACTIONS OF CERTAIN ORGANIC CHEMICALS.
We are dealing, as the results show, with groups of chemicals, all of which, whether bacteriotropic or not, greatly inhibit the engulfing of Staphylococcus aureus by leucocytes. Not a sufficiently large number of experiments was performed in attempt to cure experimental staphylococcus infections to warrant any condusion in regard to possible therapeutic activity against this organism. How-ever, as will appear in another paper, the only group out of the seven which definitely possessed an in vivo bactericidal action against pneumococcus is that of the cinchona derivatives. Certain members of the other chemical groups studied, although bactericidal in a very high dilution, -chemicals in which the concentration of a non-lethal dose was many times greater than that required to kill multiple minimal lethal doses of organisms in vitro, -had no certain effect when bacteria and drug were injected simultaneously into the peritoneal cavity of a mouse. In fact, the treated mouse often died before the controls. If we may assume,-leaving out of consideration the practical significance of in vivo chemical destruction and excretion following the injection of the drug into the animal,-that the failure of these chemicals to exhibit a benign influence on a systemic infection in cases in which the drug can be used in a bactericidal dilution, is due to their antiphagocytic property, only one step has been taken in analysis of the factors vital for the defense of the animal against a specific microorganism. Why do these chemicals inhibit leucocytic activity? Is it because of their influence upon complement, opsonin, or the leucocyte itself, or some special one function that determines the ability to ingest bacteria? Only further work can definitely settle this question and also determine whether or not such an analysis would be of practical importance in a rational development of chemotherapy. The ideal chemotherapeutic agent may be one that has an in vivo bactericidal potency and a negligible or stimulatory phagocytic action in doses non-lethal for the experimental animal. However difficult such a drug may be to find, it seems unlikely that the ultimate success in chemotherapy will be so simple. Again, it is conceivable that a secondary action of a drug, although leucocytotropic and not bacteriotropic, may bring about conditions in the animal body that will enable it to throw off the invading organism. Or finally, a drug compatible with the forces necessary to the host's defense and possessing in vivo bactericidal action to a greater or less degree may be the chemical sought for, the goal toward which we should strive, to achieve a rational chemotherapy for infectious diseases.
Laboratories of The Rockefeller Institute for Medical Research.
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LD
Felton
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Dougherty