In addition to our classic rodent models of inflammatory disease for your studies, we can apply sophisticated in vivo imaging modalities, 14-color flow cytometry, and Luminex multi-analyte profiling to interrogation of the models.

Models of Inflammation:

Rheumatoid Arthritis (RA)

Rheumatoid Arthritis Inflamation
Rheumatoid Arthritis Inflamation

RA is traditionally considered a chronic, inflammatory autoimmune disorder that causes the immune system to attack joint tissues. Once triggered, the immune response causes inflammation of the synovium, leading to edema, vasodilation, and infiltration by activated T-cells. There is currently no known cure, and current treatments focus on alleviating symptoms. One potential reason for the lack of treatments is the limitations of available preclinical animal models. Each model has strengths and weaknesses when compared with the human disease aspects.

In vivo imaging-based protocols provide an opportunity to quantify both the acute and chronic aspects of RA. Imaging readouts provide more accurate and more rapid, disease and response assessment.

Our validated imaging methods in RA models include:

  • Fluorescence imaging of:
    • Cathepsin activation
    • MMP activation
    • Bone metabolism
  • 19F MR imaging of macrophage presence
  • FDG PET imaging of acute inflammation
  • Micro-CT imaging of bone degradation
  • SPECT imaging of Tc-99m-EC20 macrophages

Collagen Antibody-Induced Arthritis (CAIA)

This model has the advantage of inducing disease in many strains of mice that are resistant to the traditional collagen-induced form of arthritis (CIA). CAIA relies on the injection of a cocktail of monoclonal antibodies directed against type II collagen (C-II), followed by a single injection of lipopolysaccharide (LPS). In animals, a significant part of the inflammatory attack on the joints is mediated by pathogenic antibodies directed against C-II.

Collagen-Induced Arthritis (CIA)

collagen-induced arthritis inflammation
Collagen-induced arthritis inflammation

This inflammation model of rheumatoid arthritis (RA) is widely used to address questions of disease pathogenesis and to validate therapeutic targets. CIA models, in mice or rats, are performed by immunization with heterologous type II collagen (C-II) in adjuvant. Susceptibility to CIA is strongly associated with major histocompatibility complex class II genes, and the development of RA is accompanied by a robust T-cell and B-cell inflammatory response to C-II.

The chief pathological features of CIA include a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, pannus formation, cartilage degradation, erosion of bone, and fibrosis. Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin-1b (IL-1β), and interleukin-6 (IL-6) are increased in CIA similar to RA. Biological therapies designed to interfere with these mediators are active in our CIA models.

LPS-Synchronized Collagen-Induced Arthritis (CIA)

Lipopolysaccharide (LPS) is an endotoxin that binds the CD14/TLR4/MD2 receptor complex and induces a strong response from the immune system. LPS dramatically increases the secretion of pro-inflammatory cytokines in many cell types, but especially in macrophages. This model enhances CIA and produces a 100 percent incidence of arthritic symptoms in mice within 24 to 48 hours after LPS injection. Unlike the CIA model, in the LPS-synchronized CIA model, arthritis progresses rapidly, within a few hours compared to weeks. The pathological features of this model are similar to the CIA pathological features.

Carrageenan-Induced Footpad Edema (CFE)

CFE is a classic model of acute inflammation. It can be used for the assessment of the overall inflammatory process and as a method to assess acute inflammatory pain. The readout of footpad swelling is an indirect measure of inflammation and the inflammatory exudate in the paw can be collected and examined. The pathological features of this model include acute swelling and hyperalgesia. Imaging may be used to complement traditional readouts in this model, for example, by non-invasive assessment of cathepsin, MPP, and macrophage activity.

Sponge (Air Pouch) Granuloma

The sponge (air pouch) granuloma model is a convenient, flexible model of acute inflammation. The model can be used for a functional assessment of the ability of a compound to inhibit cellular recruitment and the release of inflammatory mediators in response to an agonist. It can employ various inflammatory insults and be left in place for as little as a few hours or as long as several days. Combining traditional in vitro measures in this model with in vivo imaging biomarkers allows the assessment of cathepsin, MMP, and macrophage activity.