Fig. 3

Immunological dysfunction in SCI. After SCI, there is persistent and sustained spinal cord inflammation, characterized by a persistent release of different markers and autoantigens. This, together with autonomic and neuroendocrine dysregulation and bone marrow/lymphoid organ dysfunction, favors unresolved systemic inflammation in SCI patients. As the asterisks highlight, the persistent inflammation can manifest differently according to the level, severity, and timing of injury as well as other individual factors. For instance, low-grade chronic inflammation (LGCI) is commonly observed after SCI, which in turn is linked to systemic dysfunction and different comorbidities. Changes in circulating immune cell compartments and inflammatory mediators can be observed in acute and chronic SCI stages, and there is an interesting line of translational research aiming to study how these variations have an impact on patient clinical outcomes. SIRS generally co-occurs with CARS. Both SIRS and CARS are characterized by an abnormal cytokine profile related to non-neurogenic immunodepression. SCI-IDS has been recently recognized as a neurogenic immunodepression induced by the spinal cord. Whereas SIRS and CARS are more likely to occur in the early stages of SCI, SCI-IDS can appear in the early and chronic stages. Indeed, it is hypothesized that SCI-IDS can be a mechanism to prevent autoimmunity after SCI. Autoimmunity is a common immune dysfunction due to exposure to autoantigens related to cell death after SCI, especially in patients with less severe or lower levels of SCI. All these factors partially explain the high risk of suffering from infections and comorbidities after SCI, critically determining the recovery and quality of life of these patients. SCI Spinal cord injury; SCI-IDS Spinal cord injury-induced immune depression syndrome; SIRS Systemic inflammatory response syndrome; CARS Compensatory anti-inflammatory response syndrome; MBP Myelin basic protein; MAG Myelin-associated glycoprotein; OMgp Oligodendrocyte myelin glycoprotein; GluR Glutamate receptor; GM-1 Monosialotetrahexosylganglioside; HPA Hypothalamic–pituitary–adrenal