Rheumatoid arthritis is one of the most common forms of joint disease, affecting millions of people in the UK. It has long been known that its symptoms tend to get worse at certain times of day; for instance, sufferers typically complain of increased joint stiffness and inflammation early in the morning. A team of Manchester biologists are studying the body’s circadian clock, aiming to improve treatments and pain relief for this condition.

This team forms part of one of the largest clock research communities in Europe. One of its members is undertaking a five-year research project, funded by Arthritis Research UK, which is specifically looking at rheumatoid arthritis.

The researcher explains: “People have known for a long time about the significance of circadian clocks, but it is only over the last 10 to 15 years where they have realised that the immune system has a clock too. Current treatment options are not always effective for sufferers of rheumatoid arthritis, so there is a need to develop new strategies.”

This research specifically highlights the body clock as a key regulator of inflammation and focuses on the inflammatory pathways critical to rheumatoid arthritis, mapping out how the molecular clock regulates the inflammatory process underlying the disease.

Early findings

A number of clock proteins that regulates inflammation have already been identified, and compounds which act on these are being tested in order to identify novel anti-inflammatories.

The researcher explains: “Most cells have an instinctive clock and we are interested in how these clocks regulate inflammation and immunity. If we can understand the mechanisms by which the clock interacts with the immune system, we can identify new therapeutic targets and potentially new therapies.

"The implication is that you might start changing the time of day that drugs are administered in order to have the maximum benefit.”

The team has been using mice in their research, as the animals also show time-of-day variation in inflammatory markers.

Mice are immunised with collagen, which instigates the development of arthritis, characterised by inflammation within their limbs. Researchers can then manipulate the amount and timing of light the animals receive to see what effect environmental change has on the disease. Scientists can also carry out transgenic work and test timed dosing regimes (chronotherapy).

Although mice are nocturnal animals, preliminary findings have shown that paw swelling recedes during the night, just like in humans.

The researcher says: “This is a surprising finding, and tells us that the circadian clock suppresses inflammation during the night. If we can understand which clock proteins are regulating inflammation, that is a very significant step.”

Implications for other diseases

The team believes the findings could be applicable to other chronic inflammatory diseases, such as asthma, or chronic obstructive pulmonary disease.

Our researcher says: “Circadian rhythms affect everyone’s health and their impact on the treatment of cancer is already quite advanced, so we are taking these principles into combating other diseases.”