Effects of protein malnutrition on IL-6-mediated signaling in the liver and the systemic acute-phase response in rats

Abstract

. Effects of protein malnutrition on IL-6-mediated signaling in the liver and the systemic acute-phase response in rats. Am J Physiol Regul Integr Comp Physiol 287: R801-R808, 2004; 10.1152/ajpregu.00715.2003.-This study examines the effects of malnutrition on IL-6 signaling pathways of rats fed 2% vs. 20% casein diets for 14 days. Effects of malnutrition on the abundance and IL-6-stimulated phosphorylation of signaling proteins in the JAK-STAT and MAP kinase pathways were examined in the liver. Changes of the acute-phase response as reflected by serum ␣1-acid glycoprotein (AG), TNF-␣ (TNF), and IL-1␤ (IL-1) were compared in the two dietary groups at 0, 4, 8, 16, and 24 h after IL-6 administration. Under basal conditions, the abundance of the IL-6 receptor, gp130, JAK1, STAT1, and STAT3 proteins and levels of phosphorylation of ERK1/2 and p38 were significantly increased in the liver in the 2% casein group compared with the 20% casein group. With IL-6 stimulation, the increased phosphorylation per unit of protein of these signaling proteins was not different in the liver between the two groups. Before IL-6 stimulation, serum levels of TNF, IL-1, IL-6, and AG were significantly higher in the 2% casein group than in the 20% casein group. After bolus injection of IL-6, changes in IL-1 and AG were similar in the two dietary groups, although a slight decline in AG level was noted after 8 h of IL-6 administration in the 2% protein group. These data demonstrate that protein malnutrition produces changes in inflammation-related proteins characteristic of a low-grade systemic inflammatory response and, thus, can serve as an inflammatory stimulus. The capacity for response to IL-6 is preserved, suggesting adaptive preservation of acute-phase responsiveness during malnutrition.

Unchanged interleukin 6 level of protein and energy restricted goats during late gestation: the role of elevated blood nitric oxide

“…These conflicting results may indicate that the extent of nutrient restriction might have a significant effect on cytokine production. While the level of restriction imposed in our study was about 40% below the protein and/or energy requirements of the goats, body weight was not affected, indicating that the level of restriction was moderate compared to the acute restriction level imposed by Ling et al (2004). The lack of change in body weight might be due to the reduction of maintenance requirement of energy in PR or ER pregnant goats (Ryan et al 1993).…”

“…Nutrient restriction and cytokine production pro-inflammatory cytokines (including TNFa and IL6) compared to rats fed a 20% protein diet (Ling et al 2004). These conflicting results may indicate that the extent of nutrient restriction might have a significant effect on cytokine production.…”

IL-6 Levels, Nutritional Status, and Mortality in Prevalent Hemodialysis Patients

“…Among the various cytokines, IL-6 was found to be most closely related to mortality (3,4,6,7) and to be associated with more causes of inflammation than other cytokines and Creactive protein (CRP) (11,12). While an experimental study by Ling et al (13) suggested that protein-energy wasting (PEW) produces changes in inflammationrelated protein characteristics of a low-grade systemic inflammatory response, clinical studies (14 -16) found inflammation, PEW, and cardiovascular morbidity to be interrelated in HD patients, each additionally contributing to the high mortality in HD patients. Therefore, inflammation, as manifested by high levels of IL-6, has been reported as a possible link between PEW and increased cardiovascular morbidity and mortality in chronic HD patients (14,15).…”

Virgin Coconut Oil Compared to Corn Oil in World Health Organization Formula on Glutathione, TNF-α, and Body Weight Gain in Severe Malnourished Wistar Rat

“…3 Liver total glutathione (GSH) in severe malnourished rat decrease 65% compared to well-nourished rat. 4 This condition is similar to inflammation state. Liver GSH level has an inverse relationship with liver NF-KB activation level, increase IL-1β and TNF-α transcription.…”