Inflammatory diseases are becoming the scourge of our age just like infectious disease were the scourge of the past. The number of diseases that have a confirmed chronic inflammatory role are numerous and include: asthma, Crohn’s disease, hepatitis, atherosclerosis, and arthritis. Currently our treatments include acetaminophen (Tylenol), corticosteroids, or specific antibody’s to key inflammatory proteins. While these treatments do a decent job for many inflammatory disorders, for certain diseases like asthma and rheumatoid arthritis these drugs don’t work in many people. Scientists are constantly trying to find new treatments for inflammation that can better target many different people across many different diseases. A group of researchers from the United Kingdom may have stumbled across a discovery that could lead us to new treatments for inflammation and may make our current treatments better by altering the time of day they are given.
The researchers focused on the circadian rhythm, also known as your internal clock. Ir is found in all forms of life from plants to fungi and even in bacteria. In humans, the circadian rhythm is primarily maintained by a group of cells in the brain known as the suprachiasmatic nucleus (SCN). This cluster of cells controls the release of melatonin, a hormone that regulates sleep. Throughout the body, there are specific proteins that also cycle with the circadian rhythm, that is to say their activity or abundance increases and decreases at different times of the day. The research team noted that in patients with chronic inflammatory diseases there are often worsening of symptoms during the day but that seem to subside at night. Also, disruption of the normal circadian clock can aggravate inflammatory diseases. By focusing on rheumatoid arthritis, the researchers were able to identify a protein called Cryptochrome that seems to repress inflammation at night.
In their study, the researchers took mice and experimentally gave them arthritis and saw that the markers of inflammation (like paw swelling) were higher during the day then they were at night. If the mice were exposed to constant light, which disrupted their clocks, the inflammation was never repressed. Looking specifically at the cells in the joints of these animals, the researchers identified a cell type called the fibroblast-like synoviocyte (FLS) that had an active internal circadian rhythm. If they disrupted a specific protein in these cells, the Cryptochromes, the cells produced more uncontrolled inflammation. Finally, by activating the Cryptochromes with the drug KL001 the researchers were able to blunt inflammation in human FLS cells.
This work highlights the importance of getting a proper sleep in controlling inflammation and also suggests the possibility of targeting this class of proteins to help control inflammation during the day. Our work and home lives in the modern era tend to keep us up late and wake us early in the morning. The lack of sleep could be exacerbating many chronic diseases worldwide. This work could provide a means to treat them without needing to change our current schedule. The results also suggest that by modifying our current therapies to work in conjunction with the bodies circadian rhythm may lead to better control of inflammation and disease.
Image Credit: By Julio Rojas ; cropped by Before My Ken 14:48, 13 April 2009 (UTC) – originally posted to Flickr as Day_Sleepers, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=6511710