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

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.

Biodegradable nanoparticles targeting circulating immune cells reduce central and peripheral sensitization to alleviate neuropathic pain following spinal cord injury

“…The subacute period after SCI is defined by spinal cord neuronal and glial apoptosis, axonal demyelination, Wallerian degeneration, and glial scar evolution, with changes extending into the peripheral nervous system as a result of disrupted neuroimmune interfaces. 3,46 Surprisingly, despite the subacute reduction in tactile and cold hypersensitivity in NP-treated mice compared with PBS-treated negative controls, we did not observe significant reductions in spinal cord gene expression associated with neuropathic pain pathways 7 days after injury (Fig. 2A).…”

Patients with Chronic Spinal Cord Injury and a Long Period of Evolution Exhibit an Altered Cytokine Production by CD4 and CD8 T Cell Populations

“…Understanding the pathogenic mechanisms that condition the evolution of patients with chronic SCI is a critical objective in trying to carry out therapeutic interventions for improvement. There is increasing evidence of impaired immune systems and T lymphocytes in patients with chronic SCI [ 30 , 31 ]. In this work, we have investigated the pattern of cytokine secretion, focused on IFN-γ, IL-10, IL-17, IL-9, TNF-α, and IL-2 expression by CD4 and CD8 T lymphocytes in a large population of patients with chronic SCI stratified for periods of evolution after the acute spinal event.…”

Abnormal Characterization and Distribution of Circulating Regulatory T Cells in Patients with Chronic Spinal Cord Injury According to the Period of Evolution

“…The exact roles of Tregs in SCI are complex, and the functional implications of Treg expansion are not fully understood. Moreover, it is still unknown whether changes in Tregs cause immune dysfunction or whether they expand in response to altered immune environments [ 7 ].…”

“…Peripheral immune dysfunction is a major concern in patients with chronic SCI [ 7 ]. The immune system is recruited to the injury site in the early stages, orchestrating spinal cord repair after the traumatic event and promoting secondary mechanisms of damage [ 8 ].…”

“…T lymphocytes are major modulators of adaptative immune responses [ 19 ]. Previous works have evidenced that these cells play a pivotal role in the local and systemic changes occurring after SCI [ 7 , 20 ]. Immunologically, T cells can be classified into CD4 and CD8 T cells.…”