Infection with mycoplasma pulmonis modulates adjuvant‐ and collagen‐induced arthritis in lewis rats

Abstract

The arthritides induced in rats by complete Freund's adjuvant or native type I1 collagen are extensively studied models of inflammatory joint disease (1,2). Rats of the inbred Lewis (LEW) strain have commonly been found to be 100% susceptible to adjuvant arthritis (3), and have been reported to be 40-100% susceptible to type I1 collagen-induced arthritis (71 Animals. Specific pathogen-free, 4-week-old monis infection was found to be enzootic in our animal colony, and upon further investigation we found that both models of rat arthritis were significantly altered by this common rat pathogen. MATERIALS AND METHODS \LI *LEW rats, like rats of most other strains, are susceptible to infection with Mycoplasma pulmonis (4). Respiratory infections with M pulmonis, often clinically silent, are very common in conventional (i.e., non-barrier-maintained) rat colonies (4). We have recently observed unexpected variability in a series of experiments with both adjuvant and collageninduced arthritis; our results led us to suspect that an environmental factor might be intermittently affecting the incidence and severity of these diseases. M pul- Infection of rats with Mycoplasma pulmonis. Upon arrival, rats were bled from the retroorbital plexus and then divided randomly into 3 treatment groups: 1) uninfected, 2) infected with 3.6 x lo3 viable M pulmonis organisms intranasally, or 3) inoculated intranasally with 3.6 x lo3 heat-killed M pulmonis organisms (sham infected). The M pulmonis used was originally isolated from a rat housed in our conventional animal facility; it was identified as Mpulmonis by its reactivity with reference antiserum (supplied by Dr. J. Felle of the NIH). Organisms were grown in Friis broth (5). Stock cultures for inoculation were stored at -70°C until use. Organisms were enumerated by standard plate counts. At necropsy, the trachea was washed with 9.5 ml of broth and the aspirated material inoculated into both Friis agar and broth. Broth cultures were incubated at 35°C and agar cultures in 5% C 0 2 at 35°C. Induction of arthritis. Adjuvant arthritis was induced by a single intradermal tail injection of heatkilled Mycobacterium butyricum in 0.1 ml mineral oil, prepared as previously described (6). Native bovine type I1 collagen (7) was dissolved in 0.1M acetic acid

Yersinia associated arthritis in SHR rats: effect of the microbial status of the host.

“…Taurog et al have shown that clinically mild M pulmonis infection delays the onset and reduces the severity of experimental arthritis in rats. 9 The results were valid for adjuvant arthritis and collagen induced arthritis. Germ free F344 rats are known to develop severe adjuvant induced arthritis, whereas in the same experiments the conventional rats and the specific pathogen free rats developed considerably milder disease.…”

Long term follow up of SHR rats with experimental yersinia associated arthritis.

“…14 Mycoplasma pulmonis infection has been reported to have a suppressive effect on both adjuvant and collagen induced arthritis in rats. 15 During our study, a few rats suffered from mild upper respiratory tract symptoms. IgG antibodies against Mycoplasma pulmonis (State Veterinary Institute, Uppsala, Sweden) were detected in 15 of 33 rats tested.…”

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

“…Cytokine modulation therapies, such as anti-TNFα, anti-IL-23p19 and anti-IL22, are shown to alter disease development in preclinical and/or clinical settings [16-19]. Interestingly, other infections have been demonstrated to affect proinflammatory cytokines and CIA development [37,38]. Helminth product ES-62 can alter the Th17 network at multiple sites and ultimately protects mice from developing CIA [39].…”