Glucocorticoids mediate macrophage dysfunction in protein calorie malnutrition.
BACKGROUND
In hospitalized patients protein calorie malnutrition substantially increases the incidence of infection and death. Protein calorie malnutrition results in significant macrophage dysfunction. Whether a primary nutrient deficit or elevated glucocorticoids levels mediate this dysfunction is unclear. The aim of this study was to evaluate the neuroendocrine response to protein calorie malnutrition and its effects on macrophage function.


METHODS
By use of a murine model of protein calorie malnutrition, mice were randomized to (1) a standard 24% casein diet (control), (2) protein-free diet (PFD), (3) PFD in adrenalectomized mice, (4) PFD plus the glucocorticoid receptor antagonist RU486 (10 mg/kg), or (5) a standard 24% casein diet plus a 50 mg corticosterone pellet implanted subcutaneously for 7 days. Mice were killed after 7 days, and body weight and serum albumin and corticosterone levels were measured. Peritoneal macrophages were obtained, and stimulated superoxide and interleukin-6 productions were measured.


RESULTS
Protein calorie malnutrition significantly impaired macrophage function and elevated serum glucocorticoid levels. Blocking the stress corticosterone response with adrenalectomy or using RU486 to block corticosterone receptors prevented the impairment of macrophage function without restoring nutritional indexes (body weight and serum albumin level). Administration of glucocorticoids via a subcutaneous pellet reproduced macrophage impairment without leading to nutritional deficits.


CONCLUSIONS
The neuroendocrine systemic response to protein calorie malnutrition with elevated serum corticosterone levels is a major determinant of macrophage dysfunction in protein calorie malnutrition.
Hill
A D
AD
Department of Surgery, New York Hospital/Cornell University Medical Center, New York 10021, USA.
Naama
H A
HA
Gallagher
H J
HJ
Shou
J
J
Calvano
S E
SE
Daly
J M
JM
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001835:Body Weight; D003345:Corticosterone / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D011502:Protein-Energy Malnutrition / Q000473:pathology / Q000503:physiopathology*; D012709:Serum Albumin / Q000032:analysis; D013481:Superoxides / Q000378:metabolism
D005938:Glucocorticoids; D015850:Interleukin-6; D012709:Serum Albumin; D013481:Superoxides; D003345:Corticosterone