Elevated Bioactivity of the Tolerogenic Cytokines, Interleukin-10 and Transforming Growth Factor-β, in the Blood of Acutely Malnourished Weanling Mice

Abstract

The main objective of this investigation was to determine the influence of acute deficits of protein and energy on the blood levels of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), physiologically the main anti-inflammatory and tolerogenic cytokines. In four 14-day experiments, male and female C57BL/6J mice, initially 19 days old, consumed a complete purified diet either ad libitum or in restricted daily quantities, or had free access to an isocaloric purified low-protein diet. A zero-time control group (19 days old) was included. In the first two experiments, serum IL-10 levels were assessed by sandwich enzyme-linked immunosorbent assay (ELISA) and bioassay. The mean serum IL-10 bioactivities were higher (P < or = 0.05) in both malnourished groups (low-protein and restricted intake: 15.8 and 12.2 ng/ml, respectively) than in the zero-time and age-matched control groups (6.3 and 7.3 ng/ml, respectively), whereas serum IL-10 immunoactivity was high only in the restricted intake group (e.g., second experiment: 17.0 pg/ml vs. 5.4, 3.7, and 3.1 pg/ml in the zero-time control, age-matched control and low-protein group, respectively). The third and fourth experiments centered on plasma TGF-beta immunoactivity (sandwich ELISA) and bioactivity, respectively. The ELISA revealed a high mean plasma TGF-beta1 level (P < or = 0.05) in the low-protein group only, but TGF-beta bioactivity (beta1 isoform, although 15% beta2 in the restricted intake group) was high in both malnourished groups (8.7 and 9.3 ng/ml in the low-protein and restricted groups, respectively) relative to the age-matched control group (0.5 ng/ml). Thus, metabolically distinct weanling systems mimicking marasmus and incipient kwashiorkor both exhibit a blood cytokine profile that points to a tolerogenic microenvironment within immune response compartments. A model emerges in which malnutrition-associated immune competence, at least in advanced weight loss, centers on cytokine-mediated peripheral tolerance that reduces the risk of catabolically induced autoimmune disease, but this is at the cost of attenuated responsiveness to infectious agents.

Effector/memory T cells of the weanling mouse exhibit Type 2 cytokine polarization in vitro and in vivo in the advanced stages of acute energy deficit

“…Initial body weights did not differ among groups, and the food intakes and gains in fat and lean tissue exhibited by the age-matched control group were comparable with previous results pertaining to C57BL/6J weanlings given free access to the same complete purified diet [12,[19][20][21]25,29,30]. In addition, the malnutrition pathologies produced in this investigation were comparable with the pathologies reported in previous studies demonstrating a Type 2 cytokine-polarized serum immunoglobulin profile [12] and depression in adaptive cell-mediated inflammatory competence [18,21,25] in the same experimental systems.…”

“…It was pointed out elsewhere [12,21,23,26,29,30] that the lowprotein model of dietary imbalance used herein mimics essential features of incipient kwashiorkor, whereas the restricted-intake protocol reproduces critical features of marasmus. As expected of a model of incipient kwashiorkor [12,21,23,26,29,30], the carcass fat decrement of the 26-day low-protein model did not reach the extent of loss seen in the 14-day restricted-intake system, at least according to inspection of the results shown in Tables 1 and 2.…”

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.…”

Recent advances in understanding of interactions between genes and diet in the etiology of colorectal cancer

“…Hillyer et al [27] showed elevated bioactivity of TGF-β, in the blood of acutely protein and energy malnourished weanling C57BL/6J mice. Glucose starvation may also lead to effects on signalling.…”