Blood Corticosterone Concentration Reaches Critical Illness Levels Early During Acute Malnutrition in the Weanling Mouse

Abstract

Acute (i.e., wasting) pediatric malnutrition consistently elevates blood glucocorticoid levels, but neither the magnitude of the rise in concentration nor its kinetics is clear. Male and female C57BL/6J mice, initially 19 days old, and CBA/J mice, initially 23 days old, consumed a complete purified diet either ad libitum (age-matched control) or in restricted daily quantities (mimicking marasmus), or they consumed a purified isocaloric low-protein diet ad libitum (mimicking incipient kwashiorkor). Serum levels of corticosterone were assessed by double antibody radioimmunoassay after 3, 6, and 14 days (C57BL/6J strain) or after 6 and 14 days in the genetically distant CBA/J strain. Age-matched control groups of both strains exhibited mean corticosterone levels of 5-30 ng/ml, whereas the acutely malnourished groups exhibited mean levels of this hormone that were elevated by more than an order of magnitude as early as 3 days after initiation of weight loss. This outcome was confirmed in a second experiment in which the serum corticosterone level of C57BL/6J weanlings was examined by competitive binding enzyme immunoassay 3 and 14 days after initiation of the dietary protocols. Therefore, deficits of protein and/or energy in weanling murine systems relevant to acute pediatric malnutrition elicit early elevations in blood glucocorticoid levels to a magnitude reminiscent of critical illness and multiple trauma. The key to this novel finding was an exsanguination method that permitted accurate assessment of the blood corticosterone level of the healthy, quiescent mouse. Overall, the results of this investigation provide a new perspective on the glucocorticoids as part of the early hormonal response to acute weanling malnutrition coincident with the shift toward catabolic metabolism and the initiation of depression in cellular immune competence.

Adoptively Transferred Dendritic Cells Restore Primary Cell-Mediated Inflammatory Competence to Acutely Malnourished Weanling Mice

“…30 This proposition is based on the high blood levels of transforming growth factor-␤, 30 IL-10, 30 and glucocorticoid hormones 2,27 reported in acute prepubescent deficits of energy and/or protein coupled with evidence that these molecules are potent physiological regulators of dendritic cell maturation. 10 In the present investigation, however, the JAWS II cells evidently achieved antigen-presenting maturity after adoptive transfer regardless of the nutritional status of the recipients.…”

“…2,21 Numerous factors pertaining to, and impinging on, the T-cell compartment have been cited as decisive contributors to malnutrition-associated immunopathology, eg, profound reduction in T-cell numbers, 2 imbalances among critical cellular subsets, 2 directly depressive endocrinological influences, notably of glucocorticoids, 27 and dearth of necessary endocrinological stimuli, notably of leptin. 28 However, in the present investigation, adoptive transfer of viable, syngeneic CD3 ϩ (ie, T) cells failed to influence a cell-mediated immune response that was enhanced by an equivalent large number of syngeneic dendritic cells.…”

Protein-Energy Malnutrition Causes Deficits in Motor Function in Adult Male Rats

“…Corticosterone concentration is sensitive to any experimental manipulation that generates stress, including handling and blood sampling, and this can yield falsely high serum concentrations and increase group variability (27). Because the response to stress should be most comparable within each rat, the corticosterone concentrations measured on days 9 and 28 were expressed as a percentage of the concentrations on day 3, and the relative changes were compared ( Figure 2C).…”

Protein–energy malnutrition increases activation of the transcription factor, nuclear factor κB, in the gerbil hippocampus following global ischemia☆

“…However, additional time points will be necessary to rule out this possibility. Given the somewhat variable and unphysiologically high values obtained for serum cortisol, we will also need to address the possibility that stress-induced inflation of basal cortisol levels masked an effect of PEM as has been previously shown with acute preanesthesia stress [56,57].…”