The treatment of many autoimmune diseases focuses on resolving inflammation, often by targeting mediators that play a role initiating pathogenic inflammatory responses. These targeted agents can be highly effective against inflammation and autoimmune disease, but suppressing immune system responses also increases the risk of infection.
“What we need is a new strategy of innovative therapies to support patients and support their own endogenous mechanisms to resolve inflammatory responses,” said Andreas Ramming, University of Erlangen-Nuremberg, Germany, and part of the cluster of scientists working on the resolution of inflammation in Germany.
“The body has developed mechanisms that limit inflammatory responses to injury and allow resolution of inflammation. In chronic inflammatory rheumatic diseases, this resolution process is dysfunctional. Instead of suppressing inflammation, we may need to foster the resolution of inflammation in autoimmune disease.”
Dr. Ramming will discuss the latest findings in Interleukin-9 (Il-9), one of several cytokines that are involved in the resolution of inflammation during Resolving Inflammation in Autoimmune Disease on Sunday from 2:30 – 3:30 pm in room B304-305, Building B in the Georgia World Congress Center. Charles Serhan, PhD, DSc, Director of the Center for Experimental Therapeutics and Reperfusion Injury at the Brigham and Women’s Hospital and The Simon Gelman Professor of Anesthesia at Harvard Medical School, will discuss the latest findings in resolvins, a superfamily of pro-resolving mediators.
“This is an entirely new direction in thinking about rheumatoid arthritis,” Dr. Serhan said. “Rather than using inhibitors of the acute inflammatory response, which can lead to immune suppression, use pathways that are already in place to stimulate the resolution of inflammation. This is new terrain in biology.”
IL-9 and other pro-resolution cytokines are not new, Dr. Ramming noted, as most were first characterized in the 1980s and 1990s. What is new is the recognition of the role they can play during the resolution of inflammation. Dr. Ramming’s group uncovered a novel mechanism by which IL-9 can induce the resolution of inflammation.
“A major part of the work has been done in animal studies, but we also have quite substantial data from human patients with RA working with samples from joint biopsies and from blood samples,” he said. “We know the pathways that are involved, but there are not yet any approved drugs that affect this pathway.”
Work with resolvins has also been done primarily in mouse models of rheumatoid arthritis and osteoarthritis, Dr. Serhan noted. Marine oils are the biosynthetic precursors of the entire superfamily of pro-resolving mediators. He suggested elevated levels of resolvins acting to reduce inflammation in some patients may explain the anti-inflammatory effects seen in some clinical trials of marine oils.
It turns out that marine oils are not the only way to stimulate the production of resolvins. Electrical stimulation of the 10th cranial nerve, the vagus nerve, is also linked to the production of pro-resolving mediators that can have dramatic effects on arthritis.
Much of the work has been done in mouse models of arthritis, Dr. Serhan said. The human vagus and the mouse vagus are very similar in their physiological activity. Early work in the human vagus shows the same effects in results from stimulating the production of pro-resolving mediations as the mouse model. Human work on electrical stimulation of the vagus nerve is more advanced in other diseases than it is in either RA or OA.
Clinical trials involving resolvins to treat other inflammatory diseases are underway, he said, but there do not appear to be any trials in RA or other autoimmune conditions.
“This is a 180-degree change in thinking about how to treat inflammation and arthritis,” he said. “Our current agents, glucocorticoids, biologics that inhibit the inflammatory response, are systemic immunosuppressive agents with systemic side effects. These are local mediators that very selectively stimulate resolution, but only where inflammation is present. For the first time, we are looking at immunoresolvent therapies.”