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Evaluation of antigen-induced synovitis in a porcine model: Immunological, arthroscopic and kinetic studies

View Article: PubMed Central - PubMed

ABSTRACT

Background: Synovitis is an inflammation-related disease linked to rheumatoid arthritis, osteoarthritis, infections and trauma. This inflammation is accompanied by immune cells infiltration which initiates an inflammatory response causing pain, discomfort and affecting the normal joint function. The treatment of synovitis is based on the administration of anti-inflammatory drugs or biological agents such as platelet rich plasma and mesenchymal stem cells. However, the evaluation and validation of more effective therapies of synovitis requires the establishment of clinically relevant animal models.

Results: In this study, Large White pigs were pre-immunized to evaluate an antigen-induced synovitis. The immune monitoring of synovial fluids in this model allowed us the identification of IL-12p40 and T cell subsets as immune biomarkers. Moreover, the evolution of synovitis was performed by arthroscopic procedures and kinetic analysis. In summary, this paper describes an animal model of antigen-induced synovitis to be used in the evaluation of anti-inflammatory therapies.

Conclusions: The novelty of this paper lies in the development of a clinically relevant model of synovitis which permits the simultaneous evaluation of synovitis from an immunological, surgical and kinetic point of view.

Electronic supplementary material: The online version of this article (doi:10.1186/s12917-017-1025-4) contains supplementary material, which is available to authorized users.

No MeSH data available.


Temporal scheme of the immunization protocol and monitoring. Subcutaneous BSA injections (black arrows), intra-articular BSA injection (grey arrow), blood sampling (triangles), synovial fluid sampling (squares), pressure platform gait analysis (rhombus) and the arthroscopic surgery (circle) are shown
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Fig1: Temporal scheme of the immunization protocol and monitoring. Subcutaneous BSA injections (black arrows), intra-articular BSA injection (grey arrow), blood sampling (triangles), synovial fluid sampling (squares), pressure platform gait analysis (rhombus) and the arthroscopic surgery (circle) are shown

Mentions: For animal immunizations, a solution with 20 mg/ml of BSA (Sigma-Aldrich, St. Louis, MO, USA) was prepared and passed through a 0.2 μm sterilized microfilter. An equal volume of Freund Complete Adjuvant (FCA) (Sigma-Aldrich, St. Louis, MO, USA) was mixed with the BSA solution and emulsified. The immunization was performed by subcutaneous injection of this emulsion. A total of 0.4 ml/kg was injected on days 0, 14 and 21 (see Fig. 1). On day 28, a total of 0.5 ml of SF was aspirated from both joints (SF basal sample) and intra-articular immunizations of BSA were performed in the forelimbs. A total of 0.5 ml of BSA at 20 mg/ml was injected on the right carpal joint to induce the synovitis and 0.5 ml PBS on the left carpal joint (used as negative control).Fig. 1


Evaluation of antigen-induced synovitis in a porcine model: Immunological, arthroscopic and kinetic studies
Temporal scheme of the immunization protocol and monitoring. Subcutaneous BSA injections (black arrows), intra-articular BSA injection (grey arrow), blood sampling (triangles), synovial fluid sampling (squares), pressure platform gait analysis (rhombus) and the arthroscopic surgery (circle) are shown
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5384159&req=5

Fig1: Temporal scheme of the immunization protocol and monitoring. Subcutaneous BSA injections (black arrows), intra-articular BSA injection (grey arrow), blood sampling (triangles), synovial fluid sampling (squares), pressure platform gait analysis (rhombus) and the arthroscopic surgery (circle) are shown
Mentions: For animal immunizations, a solution with 20 mg/ml of BSA (Sigma-Aldrich, St. Louis, MO, USA) was prepared and passed through a 0.2 μm sterilized microfilter. An equal volume of Freund Complete Adjuvant (FCA) (Sigma-Aldrich, St. Louis, MO, USA) was mixed with the BSA solution and emulsified. The immunization was performed by subcutaneous injection of this emulsion. A total of 0.4 ml/kg was injected on days 0, 14 and 21 (see Fig. 1). On day 28, a total of 0.5 ml of SF was aspirated from both joints (SF basal sample) and intra-articular immunizations of BSA were performed in the forelimbs. A total of 0.5 ml of BSA at 20 mg/ml was injected on the right carpal joint to induce the synovitis and 0.5 ml PBS on the left carpal joint (used as negative control).Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Synovitis is an inflammation-related disease linked to rheumatoid arthritis, osteoarthritis, infections and trauma. This inflammation is accompanied by immune cells infiltration which initiates an inflammatory response causing pain, discomfort and affecting the normal joint function. The treatment of synovitis is based on the administration of anti-inflammatory drugs or biological agents such as platelet rich plasma and mesenchymal stem cells. However, the evaluation and validation of more effective therapies of synovitis requires the establishment of clinically relevant animal models.

Results: In this study, Large White pigs were pre-immunized to evaluate an antigen-induced synovitis. The immune monitoring of synovial fluids in this model allowed us the identification of IL-12p40 and T cell subsets as immune biomarkers. Moreover, the evolution of synovitis was performed by arthroscopic procedures and kinetic analysis. In summary, this paper describes an animal model of antigen-induced synovitis to be used in the evaluation of anti-inflammatory therapies.

Conclusions: The novelty of this paper lies in the development of a clinically relevant model of synovitis which permits the simultaneous evaluation of synovitis from an immunological, surgical and kinetic point of view.

Electronic supplementary material: The online version of this article (doi:10.1186/s12917-017-1025-4) contains supplementary material, which is available to authorized users.

No MeSH data available.