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

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.