Febrile and plasma iron responses of rabbits injected with endogenous pyrogen from malnourished patients

Abstract

The ability of human endogenous pyrogen (EP) harvested from malnourished patients (marasmic or kwashiorkor-like) to induce fever and a simultaneous hypoferremia in rabbits is described. Human peripheral blood leukocytes were obtained from malnourished adult patients before total parenteral nutrition support, and after 1 and 7 days on this therapeutic regime; the leukocytes were stimulated to produce EP in vitro and EP was injected into each rabbit. EP obtained from the leukocytes of patients with predominant protein deprivation syndromes (kwashiorkor) before nutritional support produced an attenuated fever (0.23 degrees C over 4 h) and a relatively unchanged plasma iron concentration (delta Fe = -15 microgram/100 ml over 4 h) in the rabbits. When EP was harvested from these same patients after 7 days of nutritional support therapy and was injected into rabbits, normal 4 h fevers (1.10 degrees C) and reduction in plasma iron levels (delta Fe = -97 micrograms/100 ml) occurred in the rabbits. Human EP obtained from patients with marasmus (predominant calorie deprivation syndromes) produced relatively normal fevers and changes in plasma iron levels in the rabbits, regardless of whether the samples were taken pre-total parenteral nutrition or after 1 and 7 days of total parenteral nutrition. These observations suggest that the synthesis of endogenous pyrogen by human peripheral leukocytes is sensitive to the availability of key substrates and that nutritional support therapy restores the capacity of these cells to produce EP in vitro.

Age and Protein Malnutrition: Effects on the Febrile Response

“…However, studies in our lab oratory and in other laboratories have shown that the ability of monocytes from malnour ished patients to produce IL-1 is markedly decreased [9,13,14], Our malnourished pa tients had a mean age of 60.8 years, but we could not assess the specific roles of age com bined with malnutrition in that study.…”

“…Previous studies in both humans and rabbits have shown that protein malnutrition is associated with de fects in the IL-1 mediated febrile response [7,9,13,14], In this study, we used the Fischer 344 rat model of aging to assess the influences of both age and protein malnutri tion on the febrile response. Two different pyrogenic stimuli were studied: endotoxin, in which the animal must produce IL-1 and also effect a rise in temperature through its thermoeffector system, and IL-1, which acts directly on the hypothalamus, raising the thermoregulatory set point and bringing thermoefTector mechanisms into play.…”

Inflammatory mediators in children with protein-energy malnutrition

“…18). Diminished production of endogenous pyrogens has been shown previously in animals with PEM and PEM patients (18)(19)(20). The combination of increased plasma cytokine concentrations and reduced ex vivo pro duction has been found previously in the acute stage of clinical infections (8.…”

Fever in the Elderly

“…One underlying factor which may contrib ute to a decreased febrile response in elderly hospitalized patients is poor nutritional sta tus, shown to be common in both medical and surgical patients [Bistrian et al, 1974[Bistrian et al, , 1976, Diminished LP or LEM production has been noted in protein-deprived rabbits [Hoffman-Goelz and Kluger, 1979] and in protein-calorie-malnourished hospitalized patients [Hoffman-Goetz et al, 1981 ;Keenan et al, 1982], Refeeding by hyperalimentation appeared to reverse these abnormalities.…”