Decreased peritoneal macrophage NF-kappaB translocation to the nucleus in protein energy malnutrition--a role for the glucocorticoid response?
OBJECTIVE
Protein energy malnutrition (PEM) induces immune suppression leading to increased morbidity and mortality. The mechanism(s) underlying PEM-mediated immune suppression remain unclear. Plasma glucocorticoid levels are elevated in PEM and it has been postulated that these increased levels may mediate macrophage (MØ) dysfunction in PEM. We have previously shown that nuclear factor kappa B (NF-kappaB) activation in response to LPS stimulation is diminished in peritoneal macrophages (PMØs) from PEM mice. We hypothesized that decreased NF-kappaB activation in lipopolysaccharide (LPS)-stimulated PMØs in PEM is mediated through increased circulating glucocorticoid levels.


METHODS
Mice were randomized to six groups of n = 15 each as follows: (1) control diet (24% casein) (C); (2) protein-free diet (PF); (3) mice with subcutaneously implanted corticosterone pellet on the control diet; (4) mice with subcutaneously implanted placebo pellet on the control diet; (5) adrenalectomized mice on the control diet; (6) adrenalectomized mice on the PF diet. Within each group, the mice were pair-fed for 7 days. At the end of the experimental time period, PMØs were harvested and NF-kappaB activation determined by electrophoretic mobility shift assay (EMSA).


RESULTS
Elevated circulating glucocorticoids diminished NF-kappaB activation but adrenalectomy failed to restore this diminution in a murine model of PEM.


CONCLUSIONS
NF-kappaB translocation to the nucleus in PEM is independent of elevated circulating glucocorticoid levels.
Stapleton
Philip P
PP
Department of Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA. ppstap@temple.edu
Barry
Linda K
LK
Freeman
Tracy A
TA
Mestre
Juan R
JR
Daly
John M
JM
D000315:Adrenalectomy; D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D003345:Corticosterone / Q000008:administration & dosage; D005260:Female; D005938:Glucocorticoids / Q000097:blood / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011488:Protein Deficiency / Q000378:metabolism
D005938:Glucocorticoids; D016328:NF-kappa B; D003345:Corticosterone