Modification of Host Responses to Bacterial Endotoxins

Serum from rabbits rendered tolerant or immune to 100 MPD-3/kg of endotoxin when passively transferred to normal rabbits gave partial tolerance to the standard dose of endotoxin. The same serum was fractionated by DEAE chromatography into 4 major fractions. Immunoelectrophoretic analysis indicated that the 7S gamma(2)-and the 19S gamma(1)-immunoglobulins were separated into two distinct fractions. Of the four fractions tested, only fraction IV containing 19S gamma(1)-immunoglobulm conferred complete pyrogenic tolerance to 100 MPD-3/kg of endotoxin. Additional fractionation of DEAE fraction IV by exclusion chromatography on sephadex G-200 gave 3 fractions. Of these only the first, containing 19S gamma(1)-immunoglobulin conferred complete pyrogenic and lethal tolerance to normal rabbits. There was no correlation between the quantity of O-specific antibodies and the ability to transfer tolerance. It is concluded that endotoxin tolerance involves a classical immune mechanism which includes both 19S gamma(1)-immunoglobulin specific for toxophore groups common to many endotoxins and a normally functioning RES. To avoid confusion with immunologic tolerance, it is suggested that the term endotoxin immunity be substituted for endotoxin tolerance.