title: Elevated bioactivity of the tolerogenic cytokines, interleukin-10 and transforming growth factor-beta, 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.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON Canada N1G 2W1.
authors.forename: Lyn
authors.initials: L
authors.lastname: Hillyer
authors.forename: Barbara
authors.initials: B
authors.lastname: Dao
authors.forename: Patrycja
authors.initials: P
authors.lastname: Niemiec
authors.forename: Shannon
authors.initials: S
authors.lastname: Lee
authors.forename: Mary
authors.initials: M
authors.lastname: Doidge
authors.forename: Izabela
authors.initials: I
authors.lastname: Bemben
authors.forename: Tirang
authors.initials: T
authors.lastname: Neyestani
authors.forename: Bill
authors.initials: B
authors.lastname: Woodward
mesh_terms: D000818:Animals; D003677:Deficiency Diseases / Q000097:blood* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011488:Protein Deficiency / Q000097:blood / Q000276:immunology; D020033:Protein Isoforms / Q000097:blood; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1
chemical_list: D020033:Protein Isoforms; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10