Abstract
The toxicity of the cholera vibrio seems to play an important role in the pathology of Asiatic cholera in man and the immune response to this toxicity is of some interest. The isolation and purification of the vibrio endotoxin reported in the preceding paper 1 has allowed a more precise investigation of this matter than has hitherto been possible. Certain aspects of these studies are herein reported in preliminary form.
There appears to be considerable confusion regarding the antigenicity of the cholera toxin since many workers have designated hemolytic strains as “toxic” and have worked with anti-hemolysins. Since it is now established that the “true” cholera vibrio is non-hemolytic, 2 such studies would seem to be irrelevant. Some workers, including Pottevin, 3 Horowitz, 4 Bail, 5 Hahn and Hirsch, 6 and Andu and van Niekerk 7 have reported the preparation of antisera which were protective in vivo against the lethal action of toxic extracts of the vibrios. It is generally admitted, however, that the antitoxic properties of antisera are only feeble at best. For example, Bail 8 attempted to account for the unaltered toxicity of serum-treated vibrios by the demonstration of free complement-fixing substances in immune guinea pigs infected with vibrios, these substances presumably representing uncombined toxin. According to Eisler and Kovacs 9 the toxin is not antigenic in that it is not specifically precipitated by antiserum, but adsorbed on the flocculating antigen-antibody complex.
In our experiments various preparations of endotoxin have been studied. The immunological activity of endotoxin prepared by preliminary extraction with alcohol and 3 subsequent precipitations with chilled acetone was indicated by skin reactions in immune rabbits and by specific precipitation and complement fixation with rabbit immune sera. The intradermal inoculation of 100 to 300 μg of endotoxin in 0.1 ml 25% alcoholic solution gave a skin reaction of the delayed type, appearing in 24 to 36 hours and fading appreciably in 48 hours, in immune rabbits but not in normal rabbits. An immediate toxic reaction, attributable only in small part to the alcohol and characterized by a circumscribed erythema followed by superficial necrosis, appeared in 1 to 3 hours and persisted for several days.
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