Chemokines and Disease

Acute inflammation is characterized by the rapid onset of pain, heat, redness, swelling and loss of function. When inflammation is long term, or chronic, and is directed at the body's own tissues, this can result in various forms of auto-immune diseases. Inflammatory bowel disease (IBD), rheumatoid arthritis (RA), ANCA-Associated Vasculitis (AAV), lupus and skin inflammatory diseases such as psoriasis and atopic dermatitis, diabetic nephropathy, multiple sclerosis (MS), and systemic lupus erythematosus (SLE), are all examples of chronic conditions in which an inappropriate inflammatory response underlies disease. In recent years, conditions that were not previously considered to be the result of inflammation, such as Type 2 diabetes, chronic kidney disease and cancer, have joined the long list of human diseases thought to be the result, at least in part, of uncontrolled and chronic inflammation. Many autoimmune diseases are highly debilitating, creating a significant social and financial burden. According to the National Institutes of Health, there were more than 80 clinically distinct autoimmune diseases which collectively affected as many as 23.5 million people in the United States in 2010.

Chemokines and other chemoattractants direct inflammatory responses, serving to precisely coordinate the movement of cells of the immune system. Inappropriate activity of the chemokine network is at the core of numerous autoimmune and inflammatory conditions. For example, in Crohn's disease, dysregulation of either the chemokine CCL25 or the chemokine receptor to which it binds, CCR9, is thought to selectively attract inflammatory T cells to, and subsequently attack, tissues in the digestive tract.

By selectively blocking a given chemokine and chemokine receptor combination, and largely leaving other chemokine-chemokine receptors interactions unaffected, we believe that even aggressive forms of chronic inflammation and autoimmunity can potentially be brought under control in a safe and effective manner.

In addition to its central role in autoimmune and inflammatory conditions, the chemokine system plays an important role in other diseases, such as cancer. It is known that tumors induce the expression of chemokines that are involved in promoting the growth of blood vessels that feed tumors, providing a link to the chemokine system's role in the establishment and spread of cancer. In addition, certain chemokine ligands and their corresponding receptors have been implicated in the survival, growth and metastasis of human cancer. The chemokine system is likely a more recent evolutionary branch of other chemo-attractant systems in the body such as the complement system. The complement system includes the protein C5a, which under certain conditions has pro-inflammatory effects.

^ Return to Top