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A non-inflammatory form of immune competence prevails in acute pre-pubescent malnutrition: new evidence based on critical mRNA transcripts in the mouse.

Abstract
The declining inflammatory immune competence of acute (i.e. wasting) pre-pubescent protein-energy malnutrition has been regarded as reflecting an unregulated immunological disintegration. Recent evidence, however, suggests that malnutrition stimulates a regulated immunological reconfiguration to achieve a non-inflammatory form of competence, perhaps offering protection against autoimmune reactions - the 'Tolerance Model'. Our objective was to determine the influence of acute pre-pubescent malnutrition on the expression of genes critical to tolerogenic regulation. Male and female C57BL/6J mice, initially 19 d old, consumed a complete purified diet either ad libitum (age-matched controls) or in restricted daily quantities (mimicking marasmus), or consumed an isoenergetic low-protein diet ad libitum (mimicking incipient kwashiorkor) for 14 d (six animals per dietary group). Gene expression in the spleen, typically an inflammatory organ, and in the small intestine, a site designed for non-inflammatory defence, was assessed by real-time quantitative RT-PCR, and normalised to β-actin. In the spleen of the malnourished groups, both IL-10 and transforming growth factor-β1 mRNA expression increased compared with controls (P < 0.05), whereas mRNA expression of IL-12p40 decreased (P < 0.05). Conversely, malnutrition exerted no influence on the expression of mRNA for these cytokines in the small intestine (P>0.05). Moreover, forkhead box P3 mRNA expression, indicative of cell-based tolerogenic potential, was sustained in both the spleen and intestine of the malnourished groups (P>0.05). Thus, despite limited supplies of energy and substrates, the spleen shifted towards a non-inflammatory character and the intestine was sustained in this mode in advanced pre-pubescent weight loss. These findings provide the first support for the Tolerance Model at the level of mRNA transcript expression.
AuthorsJennifer M Monk, Cynthia L Richard, Bill Woodward
JournalThe British journal of nutrition (Br J Nutr) Vol. 107 Issue 9 Pg. 1249-53 (May 2012) ISSN: 1475-2662 [Electronic] England
PMID21944220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • Interleukin-12 Subunit p40
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Interleukin-10
Topics
  • Actins (metabolism)
  • Animal Nutritional Physiological Phenomena
  • Animals
  • Body Weight
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Immune System
  • Immune Tolerance
  • Inflammation
  • Interleukin-10 (metabolism)
  • Interleukin-12 Subunit p40 (metabolism)
  • Intestinal Mucosa (metabolism)
  • Intestine, Small (metabolism)
  • Kwashiorkor (immunology, physiopathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein-Energy Malnutrition (immunology, physiopathology)
  • RNA, Messenger (metabolism)
  • Real-Time Polymerase Chain Reaction
  • Spleen (metabolism)
  • Time Factors
  • Transforming Growth Factor beta (metabolism)

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