Immune system-neuroendocrine dysregulation in spinal cord injury

Abstract

Multiple communicative pathways among the nervous, endocrine and immune systems facilitate physiological immunoregulation. Spinal cord injury (SCI) patients have decreased natural (NK cell) and adaptive (T cell) immune function and reduced blood levels of cellular adhesion molecules (CAMs) that participate in immune function and wound healing. We found decreased LFA-1 and VLA-4 on peripheral blood leukocytes in SCI patients and lower levels of CAMs in SCI patients with pressure ulcers than in those without them. SCI might affect immune cells and immune responsiveness by: (1) disrupting the outflow of signals from the sympathetic nervous system to lymphoid tissues and their blood vessels as well as the returning afferent signals from these tissues to the brain; (2) immunosuppression caused by the stressors affecting SCI patients; (3) interrupting returning signals to the CNS from the periphery thereby reducing facilitation of immunoregulatory CNS neurons and decreasing their activity; or a combination of all three. SCI patients may develop dysregulation of the sympathetic nervous system that is intimately involved in immune function. Chronic stress mediates immunosuppression by corticosteroids, catecholamines, endorphins and met-enkephalin. The hypothalamus coordinates the response to stress through the release of soluble products from the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Whereas the nervous and endocrine systems are not concerned with immunological specificity, they do influence the intensity, kinetics and localization of immune responses. Products of an activated immune system may generate feedback circuits capable of inhibiting, enhancing or regulating neuronal input. Immune system cells can produce neurologically active peptides including ACTH, CRF, growth hormone, thyrotropin, prolactin, human chorionic gonadotropin, endorphin, enkephalins, substance P, somatostatin and VIP. Cytokines are likely important mediators of the HPA response to immune stimuli.