Preclinical Contract Research

Collagen-induced Arthritis (CIA)

Inflammation/Autoimmune Disease

Collagen-induced Arthritis (CIA) Models

The Collagen Induced Arthritis (CIA) model is a commonly used model as it shares immunological and pathological similarities to human RA. Arthritis is initiated by intradermal injections of Collagen Type II (CII) emulsified in Complete Freund's Adjuvant (CFA). This causes an immune response generating antibodies to CII. Therefore there is both a T cell and B cell component to the pathology. The joint destruction in collagen-induced arthritis involves cartilage destruction, bone resporption, synovial hyperplasia and periarticular cell infiltration thereby sharing many similarities to human RA.


CIA Study Details:

  • Length: 35-42 days
  • Dosing Paradigms: Prophylactic (developing or semi-established), Therapeutic
  • Dosing routes: PO, IP, SC, IV, Infusion pump
  • Controls: Dexamethasone
  • Assessments: Arthritis Score, Hind paw thickness, Body weight


Optional Assessments:

  • Circulating or tissue level Biomarker analysis (protein or mRNA)
  • Collagen antibody levels
  • Cell Populations in Spleen/Lymph Node by FACS
  • Histological/IHC assessment of joints
  • PK blood collections

Longitudinal Section of the Paw from CIA Mice Model (H&E Staining):


A-F (Vehicle Group): Severe lesions are presented in Figure A. in the tarsus (T) and in the digits (D). The boxed areas are shown in Figure B. (digits) and Figure C. (tarsus). Boxed areas in C. are presented at higher magnification in Figures D-F. There is severe inflammatory infiltration, fibrosis with loss of cartilage, and widespread destruction of tarsal and digits bones (arrows) as well as soft tissue. Many of the infiltrating cells are neutrophils.

G-K (Dexamethasone Group) The tarsus is within normal limits and is shown at higher magnification in Figures H­, I and J. The bones are intact (H,I) and joint spaces are clearly identified as well as optically empty (J). Cartilage is spanned by double arrowheads (K).


Sections of Paw from CIA Model Stained for Macrophage Marker (IHC Staining for CD206):

Figure A. Medium magnification of paw section including CD206+ cells in infiltrates within soft tissue (arrows) and in bone marrow (circle). Figure B. High magnification of CD206+ cells in bone marrow



  • mouse CIA
  • rat CIA


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preclinical collagen-induced arthritis (CIA) efficacy study



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