GLASGOW, Scotland—Interleukin-27 (IL-27), a member of the interleukin-12 family with both pro- and anti-inflammatory properties, can largely prevent the development of inflammatory arthritis if given at time of disease onset, Wanda Niedbala, MD, Foo Y. Liew, MD, from the University of Glasgow, Scotland, and colleagues report in Annals of the Rheumatic Diseases.1 The research team also included investigators from the Polish Academy of Science in Poznan, from Cardiff University in the UK, and from the University of Singapore.
“These results demonstrate that IL-27 may be a potential therapeutic agent against rheumatoid arthritis at the onset of the disease,” Dr. Niedbala said.
IL-27 in RA joints: too little, or too late?
The researchers looked for evidence of IL-27 in synovial membranes from RA patients by immunohistochemistry and by western blot. They found that not only histologic sections of pannus from RA patients stained positive for IL-27 but that IL-27 was readily detectable in all synovial tissues tested.
They used a DBA/1-susceptible murine model of collagen-induced arthritis (CIA) to study the effect of IL-27. The mice were treated with intraperitoneal injections of IL-27 daily from day 21 (the day of collagen challenge). Control mice were injected with either IL-23 or phosphate buffered saline (PBS) solution.
The authors reported, “As expected, mice treated with IL-23 developed more severe disease compared with control mice treated with PBS. In contrast, mice treated with IL-27 developed significantly reduced incidence and number of arthritic paws.” The IL-27-treated mice had less extensive mononuclear and polymorphonuclear cell infiltration into the joint, synovial hyperplasia, and joint erosion.
“Together, these data clearly demonstrate that IL-27 potently suppressed the development of CIA and such activity can prevent progression of articular damage,” they concluded. However, this worked only if the IL-27 had been given before the onset of disease at day 23. It had “little or no effect” if not given until day 24. What’s more, IL-27 treatment given on day 21 reduced levels of serum IL-6 and -17, collagen-specific immunoglobulin G2a, as well as reducing levels of interferon-gamma in spleen and lymph node cells.
Translating research into practice
IL-27 is thought to produce these reductions by blocking differentiation of IL-17-producing CD4+ T-cells (Th17). IL-27 has the dual abilities to induce Th1 cell differentiation of naïve CD4+ T-cells and to suppress production of pro-inflammatory cytokines such as IL-17. Dr. Niedbala’s data show that, at least in an animal model, it is possible to use IL-27 to downregulate IL-17 and -6 synthesis, and that this is associated with attenuation of inflammatory arthritis.
Dr. Niedbala commented, “It is of interest to note that IL-27 is detected at significant levels in the joints of RA patients. It may be that the level of IL-27 present was insufficient to suppress the Th17-driven inflammation, or that the late onset of IL-27 synthesis was unable to down regulate mature Th17 and established disease.”
Reference
1. Niedbala W, Cai B, Wei X, et al. Interleukin-27 attenuates collagen-induced arthritis [published online ahead of print January 16, 2008]. Ann Rheum Dis. 2008; doi:10.1136/ard.2007.083360. http://ard.bmj.com/cgi/content/abstract/ard.2007.083360v1?rss=1.
I cannot find the original study or please release.
HealthDay Reporter
FRIDAY, Dec. 29 (HealthDay News) -- Researchers believe they've developed an important new tool in understanding rheumatoid
The new mouse model might also help explain why women are much more prone to the crippling illness than men.
"This is a big step forward, because for the first time, we have mice that actually have the human
MrsA,
Laboratories have developed a test to measure for anti-cyclic citrullinated peptide antibody, or anti-CCP. It is now being used as a diagnostic for rheumatoid arthritis. Scientists are now finding that patients have CCP antibodies months or years prior to the illness, suggesting a way to identify the disease before it starts and perhaps offer treatments to stave off the symptoms. It turns out that those with these antibodies who also have a particular variety of HLA, a complex of genes that regulate immune function, have a 30 times higher risk of developing rheumatoid arthritis than those without these genetic risk factors.
Scientists at the University of Colorado are now analyzing the genes from 2,500 first degree relatives of rheumatoid arthritis patients and testing CCP levels to see whether there is a way to predict, based on these measurements, who will go on to develop rheumatoid arthritis.
Ultimately, understanding how the genes work to confer illness will help in the development of new treatments."
Here is the complete page, again well worth looking at and even strolling around.