The peripheral sympathetic nervous system is organised into function-specific pathways that transmit activity from the central nervous system to its target tissues. The transmission of impulse activity in the sympathetic ganglia to the effector tissues is target-cell specific and ensures that the centrally generated command is faithfully conveyed. This is the neurobiological basis of the autonomic regulatory processes in which the sympathetic nervous system is involved. Each sympathetic pathway is connected to various central circuits in the spinal cord, the lower and upper brainstem, and the hypothalamus. In addition to its conventional functions, the sympathetic nervous system is also involved in protecting body tissues from challenges arising from the environment and from within the body. This function includes the modulation of inflammation, nociceptors, and, above all, the immune system. Primary and secondary lymphoid organs are innervated by sympathetic postganglionic neurons, and processes in immune tissue are modulated by the activity of these sympathetic neurons via adrenoceptors in the membranes of immune cells. Anatomical, physiological, pharmacological, and behavioural experiments in animals support the notion that the sympathetic nervous system can influence the immune system and thus regulate the body’s protective mechanisms at the cellular level (see Besedovsky and del Rey, 1992, 1995; Hori et al., 1995; Madden and Felten, 1995; Madden et al., 1995). Control of the immune system by the sympathetic nervous system would mean that the telencephalon is, in principle, able to influence immune responses via the hypothalamus. This is an attractive idea and is advocated by several groups on the basis of clinical and experimental observations (Besedovsky and del Rey, 1992, 1995; Schedlowski and Tewes, 1999; see Ader, 2007). The anatomical evidence that the sympathetic nervous system, but not the parasympathetic nervous system, is involved in controlling the immune system is overwhelming. This applies to the innervation of primary and secondary lymphoid organs. Furthermore, pharmacological and molecular biological studies show that most immune cells have adrenoceptors (especially β2, but also α1 adrenoceptors) and that most functional processes in the immune system can be influenced (enhanced or attenuated) by adrenoceptor agonists or antagonists (Bellinger et al., 2013; Bellinger and Lorton, 2014). In view of the functional specificity of peripheral sympathetic pathways to other targets, the central question is: Are the primary and secondary lymphatic organs supplied by a sympathetic pathway that is functionally distinct from other sympathetic pathways and specifically mediates an immunomodulatory effect? Several observations reported in the literature support the idea that neuronal communication from the brain to the immune system occurs via a sympathetic final pathway that is functionally distinct from all other peripheral sympathetic pathways (such as vasoconstrictor systems, visceral secretomotor systems, and visceral motility-regulating systems). These remarks and the discussion of whether immune tissue is innervated by a sympathetic pathway that differs anatomically and physiologically from other sympathetic pathways clearly show that we are at the beginning of our studies on the relationship between the sympathetic nervous system and the immune system. The problem of how the central nervous system regulates inflammatory processes, involving the immune system, the sympathetic nervous system, and small-diameter afferent neurons that innervate body tissues, requires a multidisciplinary experimental approach.
Abstract:
The peripheral sympathetic nervous system is organised into function-specific pathways that transmit activity from the central nervous system to its target tissues. The transmission of impulse activity in the sympathetic ganglia to the effector tissues is target-cell specific and ensures that the centrally generated command is faithfully conveyed. This is the neurobiological basis of the autonomic regulatory processes in which the sympathetic nervous system is involved. Each sympathetic pathway is connected to various central circuits in the spinal cord, the lower and upper brainstem, and the hypothalamus. In addition to its conventional functions, the sympathetic nervous system is also involved in protecting body tissues from challenges arising from the environment and from within the body. This function includes the modulation of inflammation, nociceptors, and, above all, the immune system. Primary and secondary lymphoid organs are innervated by sympathetic postganglionic neurons, and processes in immune tissue are modulated by the activity of these sympathetic neurons via adrenoceptors in the membranes of immune cells. Anatomical, physiological, pharmacological, and behavioural experiments in animals support the notion that the sympathetic nervous system can influence the immune system and thus regulate the body’s protective mechanisms at the cellular level (see Besedovsky and del Rey, 1992, 1995; Hori et al., 1995; Madden and Felten, 1995; Madden et al., 1995). Control of the immune system by the sympathetic nervous system would mean that the telencephalon is, in principle, able to influence immune responses via the hypothalamus. This is an attractive idea and is advocated by several groups on the basis of clinical and experimental observations (Besedovsky and del Rey, 1992, 1995; Schedlowski and Tewes, 1999; see Ader, 2007). The anatomical evidence that the sympathetic nervous system, but not the parasympathetic nervous system, is involved in controlling the immune system is overwhelming. This applies to the innervation of primary and secondary lymphoid organs. Furthermore, pharmacological and molecular biological studies show that most immune cells have adrenoceptors (especially β2, but also α1 adrenoceptors) and that most functional processes in the immune system can be influenced (enhanced or attenuated) by adrenoceptor agonists or antagonists (Bellinger et al., 2013; Bellinger and Lorton, 2014). In view of the functional specificity of peripheral sympathetic pathways to other targets, the central question is: Are the primary and secondary lymphatic organs supplied by a sympathetic pathway that is functionally distinct from other sympathetic pathways and specifically mediates an immunomodulatory effect? Several observations reported in the literature support the idea that neuronal communication from the brain to the immune system occurs via a sympathetic final pathway that is functionally distinct from all other peripheral sympathetic pathways (such as vasoconstrictor systems, visceral secretomotor systems, and visceral motility-regulating systems). These remarks and the discussion of whether immune tissue is innervated by a sympathetic pathway that differs anatomically and physiologically from other sympathetic pathways clearly show that we are at the beginning of our studies on the relationship between the sympathetic nervous system and the immune system. The problem of how the central nervous system regulates inflammatory processes, involving the immune system, the sympathetic nervous system, and small-diameter afferent neurons that innervate body tissues, requires a multidisciplinary experimental approach. Bibliography: Jänig W. Sympathetic nervous system and inflammation: a conceptual view. Auton Neurosci. 2014 May;182:4-14. doi: 10.1016/j.autneu.2014.01.004.
