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AB0117 Collagen-Induced Arthritis in Mice as a Model of Rheumatoid Cachexia
  1. E.C. Freitas1,
  2. P.V.G. Alabarse1,
  3. P.S. Lora2,
  4. J.M. Souza1,
  5. R.C.E. Santo1,
  6. A.S. Almeida2,
  7. V.O.N. Teixeira1,
  8. L.I. Filippin3,
  9. R.M. Xavier1
  1. 1Faculdade de Medicina, Universidade Federal Do Rio Grande Do Sul, Porto Alegre
  2. 2Universidade do Vale do Rio dos Sinos, São Leopoldo
  3. 3Unilasalle, Canoas, Brazil

Abstract

Background Rheumatoid arthritis (RA) extra-articular features frequently involved metabolism alterations which in a context are known as rheumatoid cachexia. Loss of lean muscle mass, reduction of grip strength and fatigue are the most common signs in RA. Loss of body weight and reduction in food intake are not usually part of human rheumatoid cachexia, but have been demonstrated before in animal models of arthritis. Recently, Evans et al1 published a definition for cachexia that seems to fulfil rheumatoid condition. Therefore a better elucidation of rheumatoid cachexia is needed and an animal model that mimics human condition may be useful.

Objectives To explored the possibility of using collagen-induced arthritis in mice as an animal model of cachexia.

Methods 8-12 weeks male DBA/1J mice were separated in two groups: control (CO) and collagen-induced arthritis (CIA). CIA animals were immunized by intradermal injection of bovine type II collagen with complete Freund's adjuvant followed by a booster. Immunization protocol and clinical signs (arthritis score and paw edema) evaluation occur as previous described by Brand et al 20072. Animals were followed by 65 days with evaluations made in day zero and at 18, 25, 35, 45, 55 and 65 days after immunization. Rheumatoid cachexia was evaluated by body weight change (%), food intake (g), fatigue (by endurance exercise performance in minutes), grip strength (g), locomotion (cm) and relative muscle weight (muscle weight in mg divided by total animal weight g). Statistical analysis includes repeated measures analysis of variance (ANOVA) for variables with variation between time and group and t-test for variables with variation only between groups. Difference was assumed when p value were lower than 0.05.

Results Arthritis score and paw edema confirm disease in CIA group. Fatigue was higher in CIA group (lower time in endurance exercise) at the same time that grip strength and locomotion was lower (after 35 days until the end of the experiment). Relative gastrocnemius muscle weight was also lower in CIA group 3.9±0.57mg/g vs 5.0±0.61mg/g (CO). Body weight change and food intake were not statistical different within groups, however in days 25 and 35 CIA animals lost more weight than CO animals.

Conclusions These data demonstrate firstly that CIA animals show metabolic extra articular events that mimics human pathophysiology arthritis. Even though there were no difference in body weight change and food intake it reinforces the similarity among CIA animal model and human RA once this variables have the same behavior in humans. Also considering the lack of studies involving rheumatoid cachexia and the obstacle that involve this study design in humans it is essential to have a solid animal model to evaluate prospectively mechanism of rheumatoid cachexia.

References

  1. Evans WJ, et al. 2008. Cachexia: a new definition. Clinical Nutrition 27(6):793-9.

  2. Brand DD, Latham KA, Rosloniec EF. 2007. Collagen-induced arthritis. Nature protocols 2(5):1269-75.

Disclosure of Interest None declared

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