Immune Deficiency And SCI

Posted by Sam Maddox in Research News on March 28, 2016

A research report was published this month affirming what is becoming increasingly clear: spinal cord injury greatly affects the immune system, and vice versa, immune response directly affects recovery from traumatic injury.

Jan Schwab, a physician/researcher (neurologist/experimental neurologist) at the Ohio State University’s Wexner Medical Center, and who is the Scientific Director for the Wings for Life Spinal Cord Research Foundation (which partly funded the work), showed how SCI causes not only all the usual stuff, such as lack of movement and functional loss, but also “induced immune deficiency syndrome,” or in simple terms, paralysis of the immune system.

What this means is that people who sustain injuries, especially those in the high-thoracic area of the spinal cord, are more susceptible to pneumonia and other infections.

The work is framed by a bleak statistic: people living with SCI are 37 times more likely to die of pneumonia than those in the rest of the population. That is perhaps an alarming clinical shortcoming, but not as appalling as this: it was reported a year ago in the Archives of Physical Medicine that despite all we know about emergency management, early treatment and healthy living, there has been no improvement whatsoever in long-term survival for people with SCI in the past 30 years. Wow. Not what one would expect as SCI medicine has grown as a specialty. FYI, that research comes from the Life Expectancy Project in San Francisco, and is based on data from the U.S. Model Systems SCI database.

So Schwab and his group are clearly motivated to understand why the paralyzed body is less able to defend itself from infection. "Prevalent infections such as pneumonia propagate mortality and disability in spinal cord injured patients. Hence, we are trying to better understand how pneumonia affects these patients so that we can develop more effective treatment strategies to reduce mortality and improve neurological outcomes," Schwab said.

The researchers looked at how mice with spinal cord injuries were less able to fight a controlled infection compared to normal (or control) mice, which were given a minor injury of the vertebral bones but no spinal cord injury. About 86 percent of the control mice could fight the infection within the first day, whereas only 35 percent of the SCI mice could knock down the infection.

The Ohio State group wondered how the mice data sized up with human clinical records. The looked at charts from 1,221 patients in the U.S. National Spinal Cord Injury Database from 1993 to 2006. Yes, the data correlates: people with serious spinal cord injuries were more likely to develop pneumonia. They deduced that the cause was a restricted ability to engage the immune system to defend against lung infection. And, just as in the mice, the patients that did the poorest job fighting pneumonia were those with high thoracic injuries.

Here’s a brief review of the paper, published in the journal Brain.

Spinal cord injury increases susceptibility to pneumonia in a neurogenic manner – related to nerve function and not to any non-specific post-traumatic stress response.

SCI increases susceptibility to pneumonia in an injury-level dependent manner. T4 to T8 have much higher rates of pneumonia than T1 to T3. Thus, thoracic lesion-level is an independent risk factor for pneumonia in motor complete patients with spinal cord injury. Incomplete SCI showed no lesion level association to the development of pneumonia.

One may wonder, why are high thoracic injuries so susceptible to pneumonia? What about quads? The answer is somewhat complicated as it relates to activation of nerves in the sympathetic nervous system (regulating autonomic, unconscious functions); the response here has to do with the nerve roots at T8. Bundles of nerve called ganglia leave the cord here and innervate parts of the body. Ultimately, the SCI immune axis is related to the connection to the spleen, source of the immune cells that respond to body invasion by nasty pneumonia bugs. As the authors put it:

Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen.

Clinical relevance: strategies are needed to fine tune or modify immune response for certain injury levels.

Speaking of immune mods, here’s a good reason to eat more yogurt: I heard another Ohio State scientist, Phil Popovich, present data last year on the interrelationship between the nervous system, the immune system and a third major player, the biome of the intestinal tract. He showed a rather striking amount of immune system compromise directly related to SCI trauma. He called this a "dysbiosis" of the neuro-immune system; SCI actually shrinks the spleen (therefore reducing immune response and antibody protection in body) and degrades the microbiome of the gut, which, we are coming to know works in harmony with all body systems. The intestinal tract, indeed, is essential for optimal immune function. A large measure of "maladaptive plasticity" of the nervous system, in response to injury, can lead to autonomic dysreflexia, increased risk of infection and pain. But Popovich found that injured animals fed an over-the-counter probiotic (VSL 3) not only improved their gut health but also had better recovery following spinal cord injury.

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