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THU0212 Model of Arthritis with The Typical Systemic Manifestations in Wistar Rats
  1. P.F. Litvitskiy1,
  2. V.N. Sakharov2,
  3. E.I. Alexeeva3,
  4. N.A. Mayansky4
  1. 1Pathophysiology Department
  2. 2Pathophysioligy Department, I.M. Sechenov First Moscow State Medical University, Russia
  3. 3Pediatric Rheumatology Department
  4. 4Laboratory Department, Scientific Center of Children's Health, Moscow, Russian Federation

Abstract

Background Autoinflammatory component rather than autoimmune one is to be leading mechanism in the pathogenesis of the systemic juvenile idipathic arthritis (sJIA). Macrophage activation sydrome (MAS) ifatal complication of sJIA also is a result of a hyperactivation of monocytes/macrophages [1, 2]. Given those data, macrophage (M1 and M2) reprogramming becomes a very promising strategy to achieve remission of the disease. Existing animal models of arthritis (particularly collagen-induced arthritis) are not adequate for experimental implementation of this approach, because a key element of their pathogenesis is the formation of autoaggressive antibodies. For a long time, adjuvant arthritis in rats was meant to be the most close (but still not optimal) animal model to investigate the pathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis [3].

Objectives To create the model of arthritis with the typical systemic manifestations caused by the use of a macrophage M1 phenotype differentiation stimulus in Wistar rats.

Methods Day 0: Rats (8 male Wistar rats, 8 month old) were injected intracutaneously (right footpads) with 0,1 ml of complete Freund's adjuvant (CFA, 5 mg/ml, DIFCO LABORATORIES, Michigan, USA) and injected intraperitoneally (i.p.) with 5 μg/kg body weight of lipopolysaccharide (LPS, 10 μg/ml, Medgamal, Russia). In control groups equivalent volumes of physiological 0.9% sodium chloride solution were used. Day 18: rats were reinjected i.p. with LPS (10 μg/kg body weight). Day 39: rats were reinjected intracutaneously (left footpads) with 0,1 ml of CFA and reinjected i.p. with LPS (10 μg per animal).

Results The temperature over the hind paw joints was found to significantly increase (p<0,05) for at least 5 days in the group of LPS+CFA (main group) in comparison with the group of CFA only. This effect was confirmed to depend on the degree of inflammation in the joints as significant differences (p=0,019) were observed between left and right hind paws in the main group on the Day 42.

Metatarsal joint diameters were increased significantly (p<0,05) for at least 5 days (after Day 39) in the main group and remained increased (non-significantly) until the end of the study.

Pain assessment was performed by the method [4, 5], the severity of local changes in the region of inflamed joints [4]. More pronounced pain and arthritis symptoms after Day 39

Conclusions Our novel animal model of arthritis (combined stimulation by M1 stimulus LPS and CFA) is cheap and easy to reproduce. The model allows to investigate systemic mechanisms of arthritis that pathogenetically are close to the systemic manifestations of arthritis in humans.

  1. Sikora K.A., Grom A.A. Curr Opin Pediatr. 2011; 23 (6): 640–646

  2. Paediatric rheumatology ATLAS. Editors: A. A. Baranov, E. I. Alekseeva, Gedike. - Reed Elsevier. Moscow.-2010.-P.22–42.

  3. Vercoulen Y. et al. Arthritis Research & Therapy. 2009; 11: 231

  4. Darvish S.F. et al. PLoS One. 2013; 8 (11): e79284

  5. Bush K.A. et al. Rheumatology (Oxford). 2001; 40 (9): 1013–1021

Disclosure of Interest None declared

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