Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

Abstract

There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi‐ethnic cohort from the developing nation of Mauritius. Population‐based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h‐PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00‐7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.98–2.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations.

Animal models of rheumatoid arthritis: How informative are they?

“…Abatacept disrupts the interaction between CD28 (expressed on T cells) and CD80 and CD86 (expressed on APCs) using a enhanced binding homolog of CD28, CTLA-4. Abatacept is made from the extracellular portion of CTLA-4 fused to human IgG1 Fc (CTLA-4Ig) (Bevaart et al, 2010). When given to rats or mice prophylactically, CTLA-4Ig supresses disease onset in CIA and reduces proliferating T cells in the lymph nodes draining the site of immunisation (Knoerzer et al, 1995;Webb et al, 1996).…”

Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells

“…This murine disease model shares several similarities with human RA, including breach of self tolerance, generation of autoantibodies, inflammatory changes in multiple joints, and erosion of bone and cartilage accompanied by pannus formation (2). Murine CIA has been used to establish the potential efficacy of several FDA-approved RA therapies, including anti-TNF Ab, IL-1 antagonists, and methotrexate (MTX) (1,3).…”

Mobilization of natural killer cells inhibits development of collagen-induced arthritis

“…Induction of arthritis in mice after immunization with type II collagen (CII), termed collagen-induced arthritis (CIA), shares several similarities with human RA, including breach of self-tolerance, generation of autoantibodies, and the development of inflammatory changes in multiple joints (2). This animal model has been used to evaluate several FDA-approved therapies for RA, including anti-TNF Ab, IL-1 antagonists, and methotrextate (3,4). Clinically relevant features of CIA include development of enlarged and hyperactive germinal centers (GCs), T cell-dependent production of pathogenic autoantibodies, and robust inflammatory responses in synovial tissues (3).…”