KeywordsSympathetic Nervous System Vagus Nerve Nicotinic Acetylcholine Receptor Common Cold Vagal Nerve
This term refers to the modulating role of the nervous system in relation to immune functions. This modulation reflects part of the bidirectional communication between the nervous system and the immune system. Neuroimmunomodulation is possible due to the existence of receptors for neurotransmitters (e.g., norepinephrine, acetylcholine) on immune cells and due to innervation of lymph nodes by sympathetic nervous system (SNS) fibers (Felten et al. 1984). These innervating fibers influence the trafficking and proliferation of immune cells, all evidence for neuroimmunomodulation. Another more recently discovered form of neuroimmunomodulation includes the one by the vagus nerve, where its descending (efferent) branches inhibit cytokine synthesis in peripheral monocytes, via the alpha-7 nicotinic acetylcholine receptor (Tracey 2009). However, the precise process by which this occurs is still under investigation and may involve certain T cells in the spleen, which indirectly respond to vagal signals and then produce themselves acetylcholine to inhibit cytokine synthesis by macrophages (Rosas-Ballina et al. 2011). The neuroimmunomodulating role of the vagus nerve may have clinical implications since the inflammatory response is at the core of the etiology of severe chronic diseases such as cancer and coronary heart disease. Thus, vagal activity is hypothesized to possibly modulate the progress of such diseases (Gidron et al. 2005, 2007), a matter under current investigation. In cancer, for example, a new neuroimmunomodulation index, which reflects a ratio of vagal activity over inflammation, was found to predict longer survival in two fatal cancers (Gidron et al. 2016), a testimony for the clinical relevance of this topic. Neuroimmunomodulation is also manifested by the differential effects of the cerebral hemispheres on peripheral immunity. Studies have shown that the left hemisphere has immune-potentiating effects, while the right hemisphere has immunosuppressive effects (Davidson et al. 1999; Meador et al. 2004). These effects were found in animals and humans and were found to be mediated by the sympathetic response, since blocking beta-adrenergic receptors abolished differences in immunity between the hemispheres. Here too, the neuroimmunomodulatory effects of the hemispheres may have clinical roles since a shift from left to right hemisphere activity during stressful periods correlated with more reported illnesses (Lewis et al. 2007). Furthermore, in a matched prospective design, people with right hemisphere lateralization were at significantly higher risk of reporting the common cold than those with left hemispheric lateralization, independent of confounders (Gidron et al. 2010). Neuroimmunomodulation has a central role in behavior medicine, by possibly explaining how psychological factors influence the risk of disease, since the SNS, vagal nerve activity, and hemispheric lateralization are each related to psychological factors as well as to immunity and risk of certain illnesses. Research is only at the beginning of understanding these neuromodulatory links and of possibly utilizing them in the service of preventing or treating diseases.
References and Further Readings
- Gidron, Y., De Couck, M., Van Laethem, J. L., Schallier, D., De Greve, J., Mareshall, R. (2016). Paper to be presented at the PCS 2nd International Lung Cancer Symposium, Budapest.Google Scholar
- Rosas-Ballina, M., Olofsson, P. S., Ochani, M., Valdés-Ferrer, S. I., Levine, Y. A., Reardon, C., Tusche, M. W., Pavlov, V. A., Andersson, U., Chavan, S., Mak, T. W., & Tracey, K. J. (2011). Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science, 334, 98–101.CrossRefPubMedPubMedCentralGoogle Scholar