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.