• Modeling Mechanism：

  CP-20961, as a non-immunogenic synthetic adjuvant, has the following core modeling mechanism: ① It non-specifically activates antigen-processing cells, enhances cell transport within local draining lymph nodes, induces early activation of T lymphocytes (expressing IL-2 receptors), and initiates an autoimmune response; ② Activated T lymphocytes mediate inflammatory signals through lymphatic tissue, recruiting macrophages to infiltrate joint tissues. Macrophages (ED1⁺ subtype as pioneer cells) release destructive enzymes such as cathepsins B/L, triggering synovial inflammation, pannus formation, and osteochondral erosion; ③ In the later stages, T/B lymphocytes continuously infiltrate the joint, interacting with MHC class II antigen-positive cells to maintain a chronic inflammatory state, mimicking the pathological process of human rheumatoid arthritis.

• Related Products：

  CP-20961 (T15003)

• Modeling Method：

  Experimental Subject：

  Rats: Female inbred Lewis rats, body weight 140–160 g

  Dosage and Administration Route：

  Model group: CP-20961, 5 mg/animal, dissolved in 0.1 ml paraffin oil, intradermal injection at the base of the tail
  Control group: Age-matched rats, untreated or injected with equivalent volume of paraffin oil;

  Dosing Frequency and Duration Model：

  Single dose

• Validation：

  1. Behavioral Validation (Core Indicators): - Joint Swelling: Significant swelling of the hind paw appeared from day 11, reaching a peak of visible swelling on day 14, and lasting until day 32; - Arthritis Score: Based on the degree of joint swelling, erythema, and functional impairment, the model group's score was significantly higher than that of the control group (p<0.01); 2. Histopathological Validation: - Acute Phase (11-14 days): Edema appeared in the soft tissues around the joint, with a large number of polymorphonuclear cells and macrophages infiltrating; - Chronic Phase (18-32 days): Synovial hyperplasia, pannus formation, erosion of cartilage and subchondral bone, and mononuclear cell infiltration at ligament attachment points (positive H&E staining); 3. Immunopathological Validation: - Cellular Markers: ED1⁺/ED2⁺/ED3⁺ macrophages, OX-19⁺ T lymphocytes, and OX-33⁺ B cells in the joint tissue. Lymphocyte infiltration, enhanced expression of OX-6⁺ MHC class II antigen positive cells; - Lymphoid tissue: From day 4 of lymph node drainage, there was an increase in IL-2R⁺ (OX-39⁺) activated T lymphocytes, and the red pulp/white pulp ratio of the spleen was elevated.

*Precautions： Five animals were slaughtered on days 4, 7, 11, 14, 18, 21, 25, and 32 after the onset of the disease.

*References：Meacock SC,et,al. Arthritis in Lewis rats induced by the non-immunogenic adjuvant CP20961: an immunohistochemical analysis of the developing disease. Ann Rheum Dis. 1994 Oct;53(10):653-8.