Can I Check Your Inflammatory Reflex?

The realms of infectious disease and critical care medicine intersect at a place called sepsis. Sepsis is what our grandmothers called "blood poisoning" and what our ancestors before that believed was caused by evil "humors" in the body. As one of about 113 physicians with dual training in both infectious disease and critical care medicine, this disease entity is one I find extremely fascinating for obvious reasons. A good way to think of sepsis, is as the final common pathway for many infections as they increase in severity. 

Sepsis recently underwent a notable change in definition that improved the utility of the concept by reflecting state-of-the-art scientific principles. The fundamental basic definition of sepsis is dsyregulated host response to infection. When I first saw the new definition, which I found to have much more clarity than prior versions, I didn't parse every word out. However, after reading Clifford Deutschman's analysis, I am reminded of how important definitions are both for what they include and also for what they exclude.

The definition of sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. What Deutschman's piece highlights is the fact that the definition stipulates only a host response -- not which part of the host. Most people, rightly, think of the dysregulated response as largely immunologic but, like many physiological phenomenon, there's more to the story. He also goes on to point to the answer to the question of what other systems are involved. 

Tracking down his references one finds that it is the nervous system that is involved. A tantalizing aspect of this involvement is something known as "the inflammatory reflex" (sounds like a media term for an attribute of Donald Trump) as elucidated by Kevin Tracey.

This reflex involves the vagus nerve directly communicating with the immune system. This communication is two way with infection triggering "sickness behavior" such as anorexia, social withdrawal, and sleepiness. On the other side, T-cells of the immune system are influenced in order to diminish inflammation, which though essential can sometimes be overwhelming. 

The details of this interaction are endlessley fascinating and open up whole areas for intervention. Equally fascinating is understanding the evolutionary role of this pathway, which predates the immune system proper as it is present in the simple organism C.elegans which does not have immune cells. Sickness behavior is interesting in its own right and one can see how such behavior might delimit contagion and conserve metabolic resources needed to weather the infectious storm--a really cool thing to contemplate.