Effect of immunosuppression on arthritis in mice induced by Mycoplasma pulmonis.
Authors: G Taylor, D Taylor-Robinson, G Slavin
Journal: Annals of the Rheumatic Diseases (1974)

In contrast to the unknown role of mycoplasmas in the pathogenesis of rheumatoid arthritis, it is known that they produce arthritis both naturally and experi- mentally in a variety of other animals.For example, Mycoplasma hyorhinis and Mycoplasma granularum cause arthritis in swine (Ross and Switzer, 1968; Switzer, 1969; Barden and Decker, 1971), Mycoplasma gallisepticum and Mycoplasma synoviae cause arthritis in turkeys and chickens (Olson, Kerr, and Campbell, 1964; Fabjicant, 1969), and Mycoplasma arthritidis and Mycoplasma pulmonis cause arthritis in rats and mice (Findlay, Mackenzie, MacCallum, and Klieneberger, 1939; Cole, Ward, Jones, and Cahill, 1971; Barden and Tully, 1969).In rats, M. arthritidis produces an acute short-term infection, but in mice infection with this mycoplasma results in a chronic arthritis which persists for at least 9 months (Cole and others, 1971).These authors suggested that the course and histopathology of the chronic phase of this arthritis closely resembles that of rheumatoid arthritis.Likewise, Barden and Tully (1969) reported that mice infected with M. pulmonis developed a chronic arthritis, joint enlargement occurring for up to 4 months after intravenous inoculation.However, the mechanisms involved in the production of these various arthritides are unknown.Denny, Taylor-Robinson, and Allison (1972) have shown that a thymu?-dependent function is impor- tant for the development of pneumonia in micein- fected intranasally with M. pulmonis, and a similaf mechanism is involved in the development of pneumonia in hamsters inoculated intranasally with Mycoplasma pneumoniae Taylor, Taylor-Rl&inson, and Fernald, 1974).Because of these observations, we have-attempted to determine to what extent the pathological features of the arthritis produced by M. pulmonis in mice are dependent upon immunological mechanisms and have examined the effect on the arthritis of immunosuppressing mice by thymectomy and by cyclophosphamide treatment.Materials and methods M. pulmonis Strain 'JB' was obtained from Mr. P. C. T. Hannan as a broth culture after three in vitro passages from the original provided by Dr. J. Tully.The broth culture was inoculated into thallium acetate-free medium and this was incubated at 37°C for 3 days after which it was dispensed in 1 ml amounts and stored at -70°C.Dilutions of this stock culture, which contained 108 colour-changing units (ccu)/ ml, were made in PPLO broth and used as inocula for mice. MiceYoung adult male CBA and C3H mice, weighing 20-30 g, were used in all experiments and were kept in isolation.They were obtained from several sources as specific pathogen-free animals and were found to be free of detect- able mycoplasmas in the nasopharynx before use.The mice were thymectomized at 3-4 weeks of age and 2 weeks later received 850-900 r whole body x-irradiation, followed by at least 106 syngeneic bone marrow cells injected intra- venously on the same day as the irradiation.In other ex- periments mice were inoculated intraperitoneally with a single dose of 300 mg cyclophosphamide/kg body weight (Turk and Poulter, 1972) at various times before and after inoculation of the mycoplasmas.Induction of arthritis and assessment ofseverity Three to 7 weeks after irradiation mice were infected by intravenous inoculation of 0-2 ml of the stock mycoplasma culture or dilutions thereof.Mice used as controls were inoculated with 0-2 ml PPLO broth.Subjective assessment of the severity of the arthritis was made by scoring the swelling of each joint from 1 to 3. Scores for groups of mice were totalled, divided by the number of animals in each group, and recorded as the 'arthritis score'. Mycoplasma mediumLiquid medium for the isolation and growth ofM.pulmonisconsisted of Difco PPLO broth (70 ml), 25% extract of dried yeast (Distillers Co. Ltd.) (10 ml), unheated Burroughs Wellcome horse serum no. 6(20 ml), 0-1 % glucose, 0-002% phenol red, 1: 2000 thallium acetate and