COVID-19 News: Neuroimmune Interactions In The Lungs Could Be Potential Drivers Of Neurogenic Pulmonary Dysfunction With NMDA Playing A Role
: Medical researchers from the University of Texas at Dallas recently pinpointed a potential strategy for counteracting the acceleration of the illness in the lungs of COVID-19 patients.
A total of fourteen scientists from the Center for Advanced Pain Studies (CAPS), a component of UT Dallas' School of Behavioral and Brain Sciences (BBS), collaborated on a project to determine if the pulmonary issues associated with SARS-CoV-2, the coronavirus that causes COVID-19, could originate with the nervous system.
The research finding which focuses on how the immune system and nervous system interact, is published in the journal: Brain, Behavior, and Immunity
The researchers identified interactions between the immune system and nerves in the lungs that can cause rapid deterioration in a COVID-19 patient's condition.
The researchers said that some of these interactions might be countered by existing drugs.
It has been understood that severe cases of COVID-19 can have a major inflammation component that seems to start in the lungs, then affect the rest of the body. Analyzing publicly available data from patients in China, the CAPS team investigated this process as a potential case of neurogenic inflammation, in which the immune system and nervous system interact in a vicious cycle, leading to runaway inflammation.
Dr Theodore J Price, , CAPS director and corresponding author of the study told Thailand Medical News, "Most people, even biomedical researchers, do not fully appreciate how much the nervous system interacts with every organ in your body. When you have a disease, the way the immune system and the nervous system interact is very important for the outcome of the disease. The better we understand this, the better we will be at making sure that patients do not go from being pretty sick to being in the ICU and on a ventilator."
Dr Price, the Eugene McDermott Professor of neuroscience, explained that COVID-19 patients who become severely ill mainly suffer from acute respiratory distress syndrome, or ARDS.
Dr Price added, "These people cannot get enough air from breathing to saturate their blood with oxygen, and that makes them very sick. Some need ventilators; some people die from it."
Early in March, when Dr Price initiated this research, knowledge of the course of the disease was still limited but it had been noted that patients with ARDS had undergone what's known as a "cytokine storm," in which the body quickly releases too many of a broad category of signaling proteins produced by the immune system.
Assistant Professor Dr Michael Burton, co-author of the study, said the diversity of these interactions has only recently been understood.
Dr Burton said, "The prevailing school of thought in neuroimmunology used to be that immune cells signal sensory neurons to influence behavior. Recent studies have shown that the reverse also happens: Sensory neurons communicate with immune cells to control immune response. Pathogens can also interact directly with sensory neurons to help their own agenda for example like how tuberculosis binds to sensory neurons to induce coughing for its spread and survival."
Dr Burton said that this could be crucial context for the immune response in COVID-19 that is causing ARDS.
He added, "A lot of treatments try to curtail the cytokine storm by targeting the immune cells themselves. But evidence from our study shows an interaction with neurons, immune cells and other cells in the lung that could provide a novel therapeutic targeting strategy."
Dr Pradipta Ray, a BBS research scientist and lead author of the paper, directed work on the creation of a computational method to examine how these nerve cells and immune cells react.
Dr Price further added, "We've done molecular profiling on the dorsal root ganglia-the peripheral nerve cells that innervate the lungs and on immune cells from the lungs of severe COVID-19 patients in China, which were publicly available because scientists had published a paper. From that, we merged these two profiles to look at how immune cells and nerve cells might interact, creating what we call an interactome. The results were very interesting."
Significantly, in addition to the expected abundance of cytokines released by the immune cells that interacted directly with neurons, the presence of one particular protein stood out to the UT Dallas team.
Dr Price explained, "There is a striking increase in NMDA (N-methyl-D-aspartate) receptors in immune cells in the lungs that is much different than you see in other diseases. It suggests that maybe the neurons there can communicate with the immune cells via glutamate, the neurotransmitter that NMDA receptors respond to. Interrupting this interaction might lessen the damaging effect."
The possible involvement of NMDA receptors is important because drugs already exist to block them.
The study team said opportunities exist for clinical trials with in-development or existing rheumatoid arthritis drugs to treat high-risk or severe COVID-19 cases.
Dr Price further added, "There are already antagonists for NMDA receptors, so we have some targets to potentially block this neurogenic inflammation. Such drugs might need to be used in combination for treatment; however, because it's not just one simple molecule that's at the root cause-it's a whole host of them."
Though the study team established that a neuroimmune response is one way that COVID-19's most severe cases might spiral out of control, Dr Price urged caution and said more research is needed to determine whether their insights might help patients.
Dr Price said, "Our research indicates that in theory a neuroimmune process could play a huge role, and we show how that might play out. But we really still do not know to what extent neurogenic inflammation might actually cause this disease. The science around COVID-19 is happening so fast; we are learning about the disease very quickly. I am fairly confident we will learn soon if our work is going to have an impact."
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