Metabolic, neuroendocrine and immune functions in basal conditions and during the acute-phase response to endotoxic shock in undernourished rats

Chronic malnutrition is one of the most important causes of several metabol ic, immune and neuroendocrine dysfunctions. The aim of the present study wa s to determine the influence of chronic food restriction on basal neuroendo crine, immune and adipocyte functions and during the acute-phase response t o endotoxic shock in female rats. The effect of refeeding of undernourished rats on the above-mentioned functions was also investigated. For these pur poses, plasma total protein, glucose, triglycerides, ACTH, corticosterone, tumor necrosis factor-alpha (TNF) and leptin (LEP) levels were determined i n basal condition and 2 h after endotoxin (LPS; 180 mu g/kg body weight, i. p.) administration in 3 different groups: (1) well-nourished (WN) controls; (2) undernourished (UN) rats as a consequence of chronic food restriction, and (3) UN rats re-fed to restoration of their body weights in the WN rat range. The results indicate that UN rats, in comparison with WN controls, d eveloped an arrest in body weight gain as well as in basal hypoglycemia, hy potriglyceridemia, hypoleptinemia, hypercorticosteronemia and enhanced adre nal glucocorticoid content; however, no changes in basal total protein, ACT H and TNF plasma levels and in anterior pituitary ACTH concentrations were found. When endotoxic shock was induced, the LPS-induced hypoglycemia devel oped in WN rats was abolished in UN animals, and both ACTH and TNF plasma c oncentrations after endotoxin, albeit significantly (p < 0.05) higher than the respective basal values, were significantly (p < 0.05) lower in UN than in WN control rats. Despite the high basal plasma corticosterone concentra tion in UN vs. WN rats, the LPS-induced glucocorticoid release was similar in WN and UN rats. Additionally, LPS treatment did not modify basal plasma LEP levels, regardless of the group. Interestingly, UN rats fed ad libitum for 15 days restored their body weight to WN rat range values, and the vari ous metabolic dysfunctions seen in UN rats in both basal and post-LPS condi tions were fully normalized. Our results clearly indicate that chronic unde rnutrition not only affects, as earlier described, reproductive function bu t also metabolic, neuroendocrine, immune and adipocyte functions, and that the effects induced by undernutrition can be fully reversed after recovery of normal body weight. The present study strongly supports the involvement of the metabolic status in the effectiveness of the defense mechanisms deve loped in patients in inflammatory stress conditions. Copyright (C) 2000 S. Karger AG, Basel.