Decreased peritoneal macrophage NF-kappaB translocation to the nucleus in protein energy malnutrition--a role for the glucocorticoid response?

• Published in: Clinical nutrition (Edinburgh, Scotland) Vol. 23; no. 2; pp. 177 - 182
• Main Authors: Stapleton, Philip P, Barry, Linda K, Freeman, Tracy A, Mestre, Juan R, Daly, John M
• Format: Journal Article
• Language: English
• Published: England 01-04-2004
• Subjects: Adrenalectomy; Animals; Biological Transport; Cell Nucleus - metabolism; Corticosterone - administration & dosage; Female; Glucocorticoids - blood; Glucocorticoids - physiology; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - ultrastructure; Mice; NF-kappa B - metabolism; Protein Deficiency - metabolism
• ISSN: 0261-5614

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.
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).
Elevated circulating glucocorticoids diminished NF-kappaB activation but adrenalectomy failed to restore this diminution in a murine model of PEM.
NF-kappaB translocation to the nucleus in PEM is independent of elevated circulating glucocorticoid levels.