Systemic bacterial invasion induced by sleep deprivation

Systemic bacterial invasion induced by sleep deprivation

Am J Physiol Regul Integr Comp Physiol 278: R905-R916, 2000;

0363-6119/00 $5.00
Vol. 278, Issue 4, R905-R916, April 2000



Carol A. Everson1 and Linda A. Toth2

1 Department of Physiology, University of Tennessee College of Medicine and 2 Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis Tennessee 38163

Profound sleep disruption in humans is generally believed to cause health impairments.

Through comparative research, specific physical effects and underlying mechanisms altered by sleep deprivation are being elucidated.

Studies of sleep-deprived animals previously have shown a progressive, chronic negative energy balance and gradual deterioration of health, which culminate in fatal bloodstream infection without an infectious focus.

The present study investigated the conditions antecedent to advanced morbidity in sleep-deprived rats by determining the time course and distribution of live microorganisms in body tissues that are normally sterile.

The tissues cultured for microbial growth included the blood, four major organs, six regional lymph nodes, the intestine, and the skin.

The principal finding was early infection of the mesenteric lymph nodes by bacteria presumably translocated from the intestine and bacterial migration to and transient infection of extraintestinal sites.

Presence of pathogenic microorganisms and their toxins in tissues constitutes a septic burden and chronic antigenic challenge for the host.

Bacterial translocation and pathogenic sequelae provide mechanisms by which sleep deprivation appears to adversely affect health.

http://ajpregu.physiology.org/cgi/content/abstract/278/4/R905

Sleep Deprivation and Host Defense


Am J Physiol Regul Integr Comp Physiol 280: R602-R603, 2001;
0363-6119/01 $5.00
Vol. 280, Issue 2, R602-R603, February 2001
 
To the Editor: Rechtschaffen and Bergmann cite studies that they contend counter our suggestion that systemic bacterial invasion and antigenic challenge are a likely cause of physiological signs induced by sleep deprivation (5). A number of issues must be considered in the interpretation of those studies and the extent to which they are germane to the present study.
A 1989 publication by Benca and colleagues (2) reported the results of in vitro proliferation and antibody tests on spleen cells collected from rats late in the experimental period. The findings showed that as compared with the responses of yoked rats, about half of the sleep-deprived rats showed reduced cellular responsiveness and half showed greater responsiveness in both assays. Thus the effects were not consistent. Moreover, bacterial translocation is not dependent on impaired lymphoproliferation, and in vitro antibody production by B cells is not necessarily reflective of sepsis.
The report of an increased rate of regression of experimentally induced subcutaneous tumors in sleep-deprived versus yoked rats (4) is an intriguing finding, but this effect is nonspecific and could be related to metabolic rather than immunologic mechanisms. The report therefore did not influence how we interpreted our findings.
Impaired host defense, accompanied by systemic infections and the many physiological and metabolic changes associated with septic states, provides a plausible explanation for signs of sleep deprivation, including hypercatabolism, a well-known consequence of infectious disease states (1). We measured numbers of live bacteria and not the many intermediary physiological responses that would link the presence of bacteria to the development of other signs. Therefore, our study was not designed to reveal correlations that might establish relationships between bacterial invasion and the progressive development of other signs associated with chronic sleep deprivation.
In a study designed to show that elimination of aerobic bacteria does not markedly alter the physiological signs associated with chronic sleep deprivation, Bergmann and colleagues (3) administered an antibiotic cocktail to rats during the baseline period and the first 4 days of sleep deprivation.

Despite this prophylactic treatment, however, eight sleep-deprived or yoked rats were excluded from analysis due to positive bacterial cultures, suggesting that the antibiotic regimen was largely ineffective.

Data from the remaining four bacteria-negative sleep-deprived rats, combined with similar data from rats given the antibiotic cocktail late during the course of sleep deprivation, were the basis for the reported negative correlation.

An absence of positive cultures of aerobic bacteria in a subset of antibiotic-treated sleep-deprived rats does not negate the finding or the implications of positive cultures of pathogenic microorganisms in untreated or even treated sleep-deprived rats.

Furthermore, the absence of positive blood or tissue cultures in septicemic patients is a well-known clinical phenomenon and does not negate the state of sepsis.

Moreover, factors other than aerobic bacteria (e.g., endotoxins derived from gut contents or killed translocated bacteria) can cause similar metabolic derangements.

Our data indicate impaired host defense, evidenced by the presence of live bacteria in normally sterile tissues.

We hypothesize that physiological changes induced by sleep deprivation allow bacteria to leave the gut, evade antimicrobial systems, and cause transient infections and finally septicemia, which leads to the death of the animal.

We thus view the presence of bacteria as a sign of a more fundamental abnormality. Clinically significant bacterial translocation and posttranslocation survival of bacteria typically does not occur in the absence of local or systemic immune impairment.

http://ajpregu.physiology.org/cgi/content/full/280/2/R602

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