Studies of Arthritis and Other Lesions Induced in Rats by Injection of Mycobacterial Adjuvant

Abstract

Summary: A disseminated inflammatory disease affecting the joints, skin, eye and mucous membranes was produced in rats following injection with killed tubercle bacilli in oil. Intradermal inoculation and footpad inoculation in particular were more effective than other routes in producing this process. Litters of rats differed markedly in susceptibility. Animals less than 5 weeks of age appeared completely insusceptible. Rats with disease showed strong skin reactivity of the delayed type to tuberculin. Injection of tuberculin parenterally produced a transient flare-up of the disease process in the joints. Injection of tubercle bacilli in oil into diseased animals produced a very intense local reaction and, if given during the subsiding phase of the disease process, an accelerated reappearance of disease (anamnestic response). Disease production was largely suppressed by whole body irradiation (600 r). Single or repeated subcutaneous injections of tubercle bacilli or tubercle bacillus fractions, begun early in life, or a single footpad injection of bacilli in oil in the first 3 weeks of life, markedly inhibited later ability to develop the disease but did not prevent later susceptibility to allergic encephalomyelitis. Passive transfer of sensitized lymph node cells to normal, irradiated, or tolerant recipients permitted the induction of inflammatory responses to tuberculin in the ankle joints and ears. Local trauma or other nonspecific inflammation (turpentine injection) induced localization of the disease process in the affected areas. The conclusion is drawn that the disease process is a delayed hypersensitive response to a disseminated antigen probably derived from the injected tubercle bacilli.