Abstract
Simple SummarySpinal cord injury can result in an increased vulnerability to infections, but until recently the biological mechanisms behind this observation were not well defined. Immunosuppression and concurrent sustained peripheral inflammation after spinal cord injury have been observed in preclinical and clinical studies, now termed spinal cord injury-induced immune depression syndrome. Recent research indicates a key instigator of this immune dysfunction is altered sympathetic input to lymphoid organs, such as the spleen, resulting in a wide array of secondary effects that can, in turn, exacerbate immune pathology. In this review, we discuss what we know about immune dysfunction after spinal cord injury, why it occurs, and how we might treat it.Individuals with spinal cord injuries (SCI) exhibit increased susceptibility to infection, with pneumonia consistently ranking as a leading cause of death. Despite this statistic, chronic inflammation and concurrent immune suppression have only recently begun to be explored mechanistically. Investigators have now identified numerous changes that occur in the peripheral immune system post-SCI, including splenic atrophy, reduced circulating lymphocytes, and impaired lymphocyte function. These effects stem from maladaptive changes in the spinal cord after injury, including plasticity within the spinal sympathetic reflex circuit that results in exaggerated sympathetic output in response to peripheral stimulation below injury level. Such pathological activity is particularly evident after a severe high-level injury above thoracic spinal cord segment 6, greatly increasing the risk of the development of sympathetic hyperreflexia and subsequent disrupted regulation of lymphoid organs. Encouragingly, studies have presented evidence for promising therapies, such as modulation of neuroimmune activity, to improve regulation of peripheral immune function. In this review, we summarize recent publications examining (1) how various immune functions and populations are affected, (2) mechanisms behind SCI-induced immune dysfunction, and (3) potential interventions to improve SCI individuals’ immunological function to strengthen resistance to potentially deadly infections.
Highlights
Spinal cord injury (SCI) is a traumatic injury that results in disrupted bidirectional communication between higher levels of the central nervous system (CNS) and the body below the level of the injury
What may make respiratory infections deadly for SCI persons is that higher injuries above the level of thoracic segment 6 (T6) result in disruption of descending supraspinal input to sympathetic preganglionic neurons (SPNs) that innervate immune organs and modulate immune function, which we describe in more detail in a later section
~70% of immune cells reside in gut-associated lymphoid tissues (GALTs), where they respond to microbial antigens and metabolites produced in the gut and serve as the first line of defense against pathogens entering via the gastrointestinal route [143]
Summary
Spinal cord injury (SCI) is a traumatic injury that results in disrupted bidirectional communication between higher levels of the central nervous system (CNS) and the body below the level of the injury. Even when death is not the eventual outcome, pneumonia and post-operative wound infections are associated with impaired functional recovery in SCI persons [2] While this increased susceptibility to infection was historically attributed to the medical interventions routinely administered in the acute phase after. The exact roles of regulatory T cells are complex, and the functional implications of increased regulatory T cells are not fully understood It is not yet known if the increase in the CCR4+ HLA-DR+ regulatory T cells causes immune dysfunction or they expand in response to an altered immune environment. These data reveal immune dysfunction after chronic SCI in humans, and the increased activation of T cells may contribute to long-term inflammation
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