Peripheral Immune Dysfunction: A Problem of Central Importance after Spinal Cord Injury

SIMPLE SUMMARY: Spinal 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. ABSTRACT: 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.