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Prevention of death from endotoxin with antisera. II. Elimination of the risk of anaphylaxis to endotoxin.

Fatal passive anaphylaxis to endotoxin was induced in mice given rat antiserum to endotoxin. In order to remove this dangerous property of antiserum, measures were taken to eliminate anaphylaxis and restore protection. Anaphylaxis to endotoxin was prevented by Isuprel, epinephrine and reserpine and by physicochemical alteration of the serum by dilution or UV irradiation. When anaphylaxis was avoided by any of these maneuvers, the antisera prevented death from endotoxin. Separation of immune globulin fractions on Sephadex columns also eliminated the anaphylactic property and the 19S and 7S fractions of immune serum prevented death from endotoxin. The observed anaphylaxis is thought to result from antigen-antibody complexes releasing vasoactive amines. Cytophilic antibody was not involved. This solution of the problem of passive anaphylaxis to endotoxin is an essential step in preparing a safe antiserum for preventing death from endotoxin in man.