Development of an experimental animal model for reactive arthritis induced by Yersinia enterocolitica infection

We attempted to induce experimental arthritis in rats by systematically testing the effect of Yersinia infections in five strains of rats, using the intragastric, intraperitoneal, and intravenous routes of inoculation. We observed that Lewis rats which were given 10(4) to 10(5) Yersinia enterocolitica WA organisms via the intravenous route consistently developed arthritis. The arthritis was most severe at 3 weeks and subsided at 6 weeks. No arthritis was observed when this bacterial strain was administered to Buffalo, Fisher, DA, and LDA rats. No replicable bacteria were detected in the joints. This aseptic characteristic parallels that seen in the human condition and establishes this as an animal model of Yersinia-induced arthritis. The probable reason for arthritis development in only the Lewis rats became apparent when we analyzed the numbers of live bacteria in the spleens and livers of these infected animals. The arthritis-susceptible Lewis rats harbored 10-fold more bacteria than the arthritis-resistant rat strains, and this systemic infection also persisted for a significantly longer period. Speculations as to why human subjects who develop Yersinia-induced arthritis are genetically predisposed have been centered principally around the role of the HLA-B27 histocompatibility antigens. The present study reveals a heretofore unrecognized critical factor: the susceptibility of the hosts to the virulence of the infectious organisms. In addition, the present animal model will provide the necessary tool for the investigation of this and other important host and bacterial factors.