Collagen Induced Arthritis

Animal models of arthritis have been used in many different kinds of experiments, including the evaluation of novel therapies, the identification of proin-flammatory cytokines, the identification of genes associated with disease susceptibility, and in the identification of markers of disease progression (9). Collagen-induced arthritis (CIA) is probably the most widely used model for studies of therapeutic intervention although data arising from such studies should be interpreted with caution because much depends on the timing of treatment (i.e., before or after onset of arthritis). For example, a number of T-cell-targeted therapies (e.g., anti-CD4, anti-interleukin [IL]-12, CTLA4-Ig) have been shown to be effective when given at the time of immunization but ineffective when given in established disease (10-13).

CIA exhibits many pathological similarities to RA (14), including similar patterns of synovitis, pannus formation, erosion of cartilage and bone, fibrosis, and loss of joint function (15). In addition, susceptibility to both human RA and murine CIA is associated with genes encoding major histocompati-bility complex (MHC) class II molecules, implying the involvement of CD4+ T cells in the pathogenesis of both forms of arthritis. Thus, susceptibility to CIA is restricted to mouse strains bearing MHC types I-Aq and I-Ar, the mouse homologs of human leukocyte antigen (HLA)-DQ, whereas in human RA certain subtypes of HLA-DR4 and -DR1 are associated with disease susceptibility. Another similarity is that humoral responses are thought to play a significant role in the pathogenesis of both CIA and RA (14) although there is a lack of convincing data pointing to a role for type II collagen-specific autoantibodies in the majority of RA patients as elevated levels of anticollagen antibody are detected only in 10-15% of patients (16). Another extremely important feature of CIA that makes it a valid model for RA is the expression of proinflammatory cytokines, including TNFa, and IL-1P, in the joints of mice with arthritis (17).

CIA induced by immunization of DBA/1 mice with chicken, rat, or bovine type II collagen usually leads to a relatively acute and self-remitting form of arthritis in which arachidonic acid metabolites, such as prostaglandin E2, play an important pathological role in the development of arthritis. This was shown in a study in which cytosolic phospholipase A2a (cPLA2a) knockout mice were backcrossed onto the arthritis susceptible DBA/1 background. cPLA2a is responsible for releasing arachidonic acid from cell membranes, which is the first step in the production of prostaglandins and leukotrienes. The development of arthritis was profoundly inhibited in cPLA2a knockout mice compared with wild-type littermates, despite the fact that levels of type II collagen-specific antibodies were comparable in the two groups (18). However, immunization of DBA/1 mice with mouse collagen results in a more chronic form of arthritis (19-21), which is resistant to nonsteroidal anti-inflammatory drugs, such as indomethacin (21). However, the drawback to the use of autologous type II collagen is that it is less arthritogenic than heterologous collagen and therefore produces a less reproducible form of arthritis. The relative lack of arthritogenic-ity of mouse collagen has been attributed to the low affinity of specific epitope of murine collagen (CII256-270) for I-Aq, which results in a low level of CII-specific T-cell activation (22).

Natural Arthritis Pain Remedies

Natural Arthritis Pain Remedies

It's time for a change. Finally A Way to Get Pain Relief for Your Arthritis Without Possibly Risking Your Health in the Process. You may not be aware of this, but taking prescription drugs to get relief for your Arthritis Pain is not the only solution. There are alternative pain relief treatments available.

Get My Free Ebook


Post a comment