The central nervous system is not just a passive responder to the outside world, but is fully able to control many previously unanticipated physiologic responses, including immunity and inflammation," said Gary S. Firestein, M.D., Professor of Medicine, Chief of the Division of Rheumatology, Allergy and Immunology, and Director of UCSD's Clinical Investigation Institute, who led the study.
The UCSD research team found that blocking key signaling enzymes in the CNS of rats resulted in decreased joint inflammation and destruction. Their findings will be published in the September edition of the journal Public Library of Science (PLoS) Medicine.
"This is an entirely new approach," Firestein said. ¡§Instead of targeting enzymes at the actual site of disease, our hypothesis is that the central nervous system is a controlling influence for the body and can regulate peripheral inflammation and immune responses."
For many years, researchers have explored developing therapeutic targets by blocking the function of a signaling enzyme called p38 MAP kinase throughout the body. This enzyme regulates cytokines proteins released in response to stress that regulate inflammation in patients with arthritis. p38 is known to regulate production of a one particular cytokine called TNFƒÑ, and inhibitors of this cytokine are effective therapies for rheumatoid arthritis. Typically, researchers attempt to inhibit proteins in the main tissues affected by the disease, such as the joints in arthritis or the colon in inflammatory bowel disease.
UCSD's multidisciplinary research team including Linda Sorkin, Ph.D., Department of Anesthesiology and David L. Boyle, Department of Medicine thought that the CNS might play a more important role in controlling the symptoms of rheumatoid arthritis than previously believed. To test their hypothesis, the researchers studied the p38 MAP kinase signaling in rat spinal cords.
The scientists used a novel drug delivery system to administer miniscule amounts of a compound that blocks these signals only in the CNS and then determined the influence of the treatment on peripheral arthritis.
We observed that the p38 signal is turned on, or activated, in the central nervous system during peripheral inflammation," Firestein said. "If we blocked this enzyme exclusively in a highly restricted site but not throughout in the body, inflammation in the joints was significantly suppressed."
Not only were clinical signs of arthritis diminished in those rats where p38 inhibitors were administered into the spinal fluid, but damage to the joint was also markedly decreased. The same dose of the inhibitors administered systemically had no effect.
The group also explored whether TNFƒÑ might also play a role in this observation. Using a TNF-inhibitor that is approved for use in rheumatoid arthritis and is usually given throughout the body, the scientists showed that delivering small amounts of this agent into the central nervous system also suppressed arthritis and joint destruction in the rats. They proposed that inflammation in the joints increases TNF production in the central nervous system, which, in turn, activates spinal p38. By blocking this pathway only in the spinal cord, they observed the same benefit that was normally achieved by treating the entire body with much higher doses.
The novel mechanism could have therapeutic implications related to the design and delivery of anti-inflammatory drugs, and may be related to the way pain signals are perceived by the brain. The study also shows that the interactions between the CNS and the body are highly complex.
Debra Kain | EurekAlert!
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
13.07.2018 | Event News
13.07.2018 | Materials Sciences
13.07.2018 | Life Sciences