Acute downregulation of antibody production against antigens draining from the spinal subarachnoid space following spinal cord injury: Mediation by systemic catecholamines.

摘要

Traumatic spinal cord injury continues to be a significant problem in the United States. The estimated incidence of SCI is approximately 10,000 new cases per year. Besides the disruption of neuronal and vascular structures, spinal cord injury induces a pronounced inflammatory response that appears to be responsible for much of the secondary damage to intact tissue surrounding the injury site. Although over 89% of spinal cord injuries affect the cervical and thoracic regions (Nobunaga et al., 1999) and therefore compromise sympathetic outflow that originates in the spinal cord, no studies have been performed to investigate the potential impact of an altered sympathetic function on the inflammatory response that follows spinal cord injury.Recently, the notion that autoimmune cells and autoantibodies play an important role in neuronal repair (Moalem et al., 1999 Moalem et al., 2000a Huang et al., 1999 Asakura et al., 1996 Annunziata et al., 1997 Asakura et al., 1998) has made it interesting to investigate whether beneficial immune responses against central nervous system antigens can be mounted following a spinal cord injury. The functional status of the sympathetic system is relevant during autoantibody responses because of studies indicating that norepinephrine and neuropeptides released by sympathetic nerve terminals in the lymphoid organs play a key role in modulating inflammatory responses, not only against foreign (Alaniz et al., 1999 Williams et al., 1981), but also against self-antigens (Chelmicka-Schorr et al., 1988 Chelmicka-Schorr et al., 1989 Chelmicka-Schorr et al., 1992). Moreover, norepinephrine appears to be essential in the formation of at least some types of antibody responses (Kohm and Sanders, 1999). Following SCI a surge of catecholamines is released both locally within the parenchyma of tissues innervated by the sympathetic nervous system, including the lymphatic organs, and systemically by the adrenal glands. Within minutes of this surge of catecholamines, a quiescence of the sympathetic system ensues and is characterized by a chronic impairment of centrally-mediated NE release from sympathetic terminals. Both the acute systemic surge of catecholamines and the chronic absence of NE release can have dramatic effects on immune responses acutely after injury, especially on antibody responses. Thus as a first step to tackle this question, the aim of this thesis was to investigate the possibility that a high injury to the spinal cord decreases the animal's ability to produce antibody responses as a result of the acute and chronic effects of SCI on the sympathetic system.