The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 105, 591-614, Copyright, 1957, by The Rockefeller Institute for Medical Research New York

ARTICLE

EXPERIMENTAL STUDY OF DIPHTHERITIC POLYNEURITIS IN THE RABBIT AND GUINEA PIG : I. IMMUNOLOGIC AND HISTOPATHOLOGIC OBSERVATIONS



Byron H. Waksman M.D.1, Raymond D. Adams M.D.1, and Herbert C. Mansmann Jr. M.D.1

1 From the Departments of Bacteriology and Immunology and of Neurology-Neuropathology, Harvard Medical School, and the Neurology Service, Massachusetts General Hospital, Boston

Diphtheritic neuritis was produced in rabbits and guinea pigs by injection of underneutralized toxin-antitoxin mixtures. The disease is a progressive, ataxic paresis related in severity to the dose of injected toxin-antitoxin. Cerebrospinal fluids of rabbits with this disease showed "albuminocytologic dissociation" similar to that found in the same disease in man. Histologically the disease is a progressive demyelination of the peripheral nervous system, un-accompanied by axis cylinder damage or inflammation. It involves the spinal roots and sensory ganglia in the rabbit, the peripheral nerves in the guinea pig. Diphtheritic neuritis can be distinguished from experimental allergic neuritis in the rabbit and guinea pig on both clinical and histological grounds. The rabbit disease is however an excellent model of diphtheritic neuritis in man.

In the animals with diphtheritic neuritis, studied in the present work, there was vigorous production of circulating antitoxin and infrequently complement-fixing antibody to horse serum proteins. No antibody against rabbit spinal cord or sciatic nerve was demonstrated. Skin reactivity to both rabbit nerve suspension and diphtheria toxoid was present at 1 to 2 weeks following inoculation and reached a maximum well before the peak of antitoxin response. These reactions did not seem to be typical delayed reactions. No correlation existed between the development of diphtheritic polyneuritis and any of these immunologic events or the circulating complement level, either in time or in degree. Treatment of rabbits with 400 r whole body irradiation 48 hours before inoculation resulted in severe leukopenia lasting about 3 weeks, delay of antitoxin formation with considerable reduction of peak titers, and some decreased skin reactivity to toxoid. It had no effect on the disease process. It is concluded that diphtheritic polyneuritis is produced by a non-immunologic mechanism, e.g., direct toxicity.

 Submitted on January 13, 1957


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