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Department of Microbiology and Immunology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD
2To whom correspondence should be addressed. E-mail: wrbeisel{at}aol.com.
The bidirectional interrelationships between host nutrition and infectious illnesses are exceedingly complex. Despite many studies conducted over the years, these multifaceted associations are still incompletely understood. This Symposium was planned to shed new light on certain of these relationships. Accordingly, Dr. Scrimshaw reviews general historical concepts, Drs. Powanda and Beisel focus on the effects of several infections on protein and energy metabolism, Dr. Rosenberg and his colleagues discuss the metabolic and nutritional consequences of diarrhea, and Dr. Keuch evaluates the interactions between malnutrition and the immune system.
My own involvement in this field has covered each of the above topics. This interest began in the late 1950s when, as Chief of the Metabolic Research Department at Walter Reed Army Hospital, I was directed to lead a small Army team to study an outbreak of cholera in Thailand. We joined up with Drs. Phillips and Watten of the U.S. Navy, and with the Thailand Chief, Dr. Chanyo Benyajati. Dr. Benyajati had obtained full residency training in the United States and spoke perfect English.
We obtained numerous biopsies throughout the intestinal tracts of cholera patients using the biopsy capsule invented by Dr. William Crosby, Chief of Medicine at Walter Reed Army Institute of Research. All biopsies showed that the intestinal mucosa was intact, although inflamed (1
). The mucosa had not sloughed off, which until then was believed to be the cardinal pathological feature of cholera.
Stool measurements from the cholera patients showed the massive, expected losses of intestinal water, Na and Cl, but there were also large intestinal losses of K and bicarbonate (2
). These intestinal losses of bicarbonate accounted for the systemic acidosis experienced by cholera patients.
Immediate and massive intravenous therapy was consistently life-saving. The diarrhea stopped spontaneously within a few days. Antibiotics were not necessary in our patients. These findings forever changed the textbook concepts about cholera. Cholera is no longer considered to be a fatal illness. Because of these, and subsequent studies, the lives of half a million cholera patients have been spared, worldwide, each and every subsequent year.
Based on the successes of these studies, the Army then assigned me to Ft. Detrick, MD, where research volunteers were being exposed to a variety of infectious organisms and toxins as part of a vaccine development program. These volunteers were all young Seventh-Day Adventist soldiers. The program itself was monitored by a Committee consisting of a dozen of our nation’s senior Academic Professors of Infectious Diseases, and by the Seventh-Day Adventist church as well.
I was able to conduct over 150 complete metabolic balance studies (3
,4
) on these volunteers. Each study began 2 wk before the planned date of exposure of a volunteer to a cultured microorganism or a bacterial toxin. A study then lasted 
2 wk after recovery from illness. Control studies included identical metabolic balance studies 1) during induced, noninfectious fevers; 2) during "pair-fed" dietary deprivation, which matched the self-imposed reduction in food intake of volunteers with acute tularemia; and 3) during a course of paired antibiotic "therapy" given to healthy volunteers who had not been exposed to any illness.
These studies demonstrated that two major nutritional consequences resulted from various infectious illnesses. First, there were large absolute losses (i.e., wastage) of nutrients from the body. Second, there were numerous functional changes in the localization and metabolism of nutrients throughout the body.
Absolute losses of body nutrients caused by infection included sodium, potassium, chloride, sulfur, zinc, nitrogen and phosphate.
Functional changes in metabolism involved the uptake, diversion and/or sequestration of various body nutrients. In addition, body nutrients were taken up by various infecting microorganisms or parasites. Such functional metabolic changes were similar during induced fever (3
,4
), as well as all symptomatic bacterial, viral and toxic illnesses. These changes did not begin during the incubation period of any infection, but appeared, and became maximal, during the acute phase of the illnesses that were studied.
Many endocrine responses were also noted (5
–7
), but none of these responses, alone or in combination, could account for either the absolute losses or the functional changes in metabolism of the aforementioned elements.
Glucose tolerence tests during fever became typical of those seen during diabetes. Changes were also seen in the metabolism of lipids (8
), vitamins (9
) and trace elements (10
). Metabolic changes were prolonged during chronic illnesses, but minimal or absent during subacute infections.
Because hormonal changes could not explain the metabolic effects, or losses of body nutrients during infection, we searched for some other, yet unknown, hormonelike factor that might be responsible. Indeed, we found that a protein released from WBCs initiated all of these changes (11
,12
). We named this protein leucocytic endogenous mediator (LEM). It stimulated all of the recognized metabolic and immunologic effects (13
) of infection in laboratory animals, and in volunteer subjects as well. However, in a few years, an international committee included our endogenous mediator under the new name of interleukin-1.
After these studies began, I was able to have the Army assign a large series of physicians, veterinarians and Ph.D. scientists to this project. With their help, the diverse findings from these studies were reported in numerous comprehensive papers, some of which are included in the reference list of this paper. Sadly, I rarely, if ever, see any of these papers being cited in today’s literature. I fear, therefore, that many modern-day nutritional scientists are not aware of these unique data. In closing, I must thank all the members of my staff, along with our research volunteers, for participating in these studies and for the successes we achieved.
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FOOTNOTES |
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LITERATURE CITED |
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 TOP LITERATURE CITED |
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1. Gangarosa, E. J., Beisel, W. R., Benyajati, C., Sprinz, H. & Piyaratn, P. (1960) The nature of the gastrointestinal lesion in Asiatic cholera and its relationship to pathogenesis: a biopsy study. Am. J. Trop. Med. Hyg. 9:125-135.
2. Beisel, W. R., Watten, R. H., Blackwell, R. Q., Benyajati, C. & Phillips, R. A. (1962) The role of bicarbonate pathophysiology and therapy in Asiatic Cholera 1962NAMRU-2 Research Report MR005 09-1040.
3. Beisel, W. R., Sawyer, W. D., Ryll, E. D. & Crozier, D. (1967) Metabolic effects of intracellular infections in man. Ann. Intern. Med. 67:744-779.
4. Beisel, W. R., Goldman, R. F. & Joy, R.J.T. (1968) Metabolic balance studies during induced hyperthermia in man. J. Appl. Physiol. 24:1-10.
5. Beisel, W. R., Bruton, J., Anderson, K. D. & Sawyer, W. D. (1967) Adrenocortical responses during tularemia in human subjects. J. Clin. Endocrinol. Metab. 27:61-69.[Medline]
6. Shambaugh, G. E., III & Beisel, W. R. (1967) Insulin response during tularemia in man. Diabetes 16:369-376.[Medline]
7. Shambaugh, G. E., III & Beisel, W. R. (1967) Early alterations in thyroid hormone physiology during acute infection in man. J. Clin. Endocrinol. Metab. 27:1667-1673.[Medline]
8. Beisel, W. R. & Fiser, R. H., Jr (1970) Lipid metabolism during infectious illness. Am. J. Clin. Nutr. 23:1069-1979.
9. Beisel, W. R., Herman, Y. F., Sauberlich, H. E., Herman, R. H., Bartelloni, P. J. & Canham, J. E. (1972) Experimentally induced sandfly fever and vitamin metabolism in man. Am. J. Clin. Nutr. 25:1165-1173.[Abstract]
10. Pekarek, R. S., Burghen, G. A., Bartelloni, P. J., Calia, F. M., Bostian, K. A. & Beisel, W. R. (1970) The effect of live attenuated Venezuelan equine encephalomyelitis vaccine on serum iron, zinc, and copper concentrations. J. Lab. Clin. Med. 76:293-303.[Medline]
11. Wannemacher, R. W., Jr, DuPont, H. L., Pekarek, R. S., Powanda, M. C., Schwartz, A., Hornick, R. B. & Beisel, W. R. (1972) An endogenous mediator of depression of amino acids and trace metals in serum during typhoid fever. J. Infect. Dis. 126:77-86.[Medline]
12. Pekarek, R. S., Wannemacher, R. W., Jr, Chapple, F. E., III, Powanda, M. C. & Beisel, W. R. (1972) Further characterization and species specificity of leukocytic endogenous mediator (LEM). Proc. Soc. Exp. Biol. Med. 141:643-648.[Medline]
13. Beisel, W. R. (2002) Micronutrients and HIV Infection. Friis, H. eds. CRC Series in Modern Nutrition 2002:23-42 CRC Press Washington, D.C. .
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