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Abstract
Cytokine production by the immune system contributes importantly to both health and disease. The nervous system, via an inflammatory reflex of the vagus nerve, can inhibit cytokine release and thereby prevent tissue injury and death. The efferent neural signaling pathway is termed the cholinergic antiinflammatory pathway. Cholinergic agonists inhibit cytokine synthesis and protect against cytokine-mediated diseases. Stimulation of the vagus nerve prevents the damaging effects of cytokine release in experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, arthritis, and other inflammatory syndromes. Herein is a review of this physiological, functional anatomical mechanism for neurological regulation of cytokine-dependent disease that begins to define an immunological homunculus.
Authors
Kevin J. Tracey
Kevin Tracey’s Contextual View of Disease
Submitter: Ben Kavoussi | kavoussi@ucla.edu
Santa Monica, CA
Published March 5, 2007
In the Feb 2007 issue of the Journal of Clinical Investigation, while setting the historical perspectives of the cytokine theory of disease, Kevin Tracey also made a few epistemological and historical comments that warrant being further discussed.
By referring to Claude Bernard’s notion of equilibrium in the ‘milieu interieur,’ Tracey is actually referring to what the epistemologist Paul Unschuld calls a ‘functional-individualistic’ view of disease, a notion reminiscent of the pre-modern European concepts of humoral pathology or the Chinese phases/elements theory. In this approach, the individual is perceived as a system of interlinked functional units, which work in unison in order to sustain life in a specific environment. To this ‘organic’ view, opposes an ‘ontological’ view that perceives disease as the intrusion of a malignant force, or entity, that exists independently of its manifestations, and is of ancestral, demonological, miasmatic, parasitic, microbial, or of any other exogenous origin. Both views have coexisted throughout the history of medicine, and physicians have favored one or the other, depending on the prevalent worldviews. For instance, as Unschuld writes, when in 19th century Ferdinand Hebra identified the mite as causing scabies, when Agostino Bassi identified a fungus as causing silkworm disease, and when Jacob Hanley considered bacteria as cause of disease, these ideas were rejected, not because they were new and revolutionary, but because they involved ideas of malignancy which were then considered to be old and outdated!
The rebirth of the ontological perspective, or the ‘germ theory,’ in the 19th century was predominately due to Louis Pasteur, Robert Koch, and others radical bacteriologists who were able to establish indisputable links between germs and disease trough observation and experimentation. Nonetheless, Unschuld recounts that the germ theory did not discourage the advocates of the functional-individualistic view who opposed the claims of radical bacteriology, and held that something must be internally wrong with an organism for it to become susceptible to disease. In the mid-20th century this argument contributed to Hans Selye’s, Georges Canguilhem’s and Owsei Temkin’s whole patient and contextual approaches to disease (and thus medicine).
Tracey’s advocacy of a contextual-individualistic view would hopefully facilitate a better use of dietary supplements, mind-body medicine, acupuncture, and many other time-honored modalities, and would allow patient-centered therapies to play a more significant role in the pluralistic and integrative medicine of our postmodern era where traditional, modern, late modern and postmodern attitudes all rub elbows in the same culture.
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ISSN: 0021-9738 (print), 1558-8238 (online)