Control of immunity via nutritional interventions.

Nutrition affects all physiological processes including those linked to the development and function of our immune system. Here, we discuss recent evidence and emerging concepts supporting the idea that our newfound relationship with nutrition in industrialized countries has fundamentally altered the way in which our immune system is wired. This will be examined through the lens of studies showing that mild or transient reductions in dietary intake can enhance protective immunity while also limiting aberrant inflammatory responses. We will further discuss how trade-offs and priorities begin to emerge in the context of severe nutritional stress. In those settings, specific immunological functions are heightened to re-enforce processes and tissue sites most critical to survival. Altogether, these examples will emphasize the profound influence nutrition has over the immune system and highlight how a mechanistic exploration of this cross talk could ultimately lead to the design of novel therapeutic approaches that prevent and treat disease.

Non-specific immunity and ketone bodies. I: In vitro studies on chemotaxis and phagocytosis in ovine neutrophils.

The in vitro effects of the ketone bodies beta-OH-butyrate (2.4 or 4.8 mmol/l) and acetoacetate (2.4 or 4.8 mmol/l) on the uptake of latex particles (1.09 microns) and chemotaxis were investigated in ovine neutrophils. Because the acetoacetate used was a lithium salt, the effect of 2.4 or 4.8 mmol/l lithium chloride was also tested. Neutrophils from eight non-lactating, non-pregnant ewes were studied. The uptake of latex particles, as measured by a spectrophotometric method, showed wide individual variation. The phagocytotic activity was unaffected by 2.4 mmol/l ketone bodies and LiCl, but it was significantly inhibited by 4.8 mmol/l beta-OH-butyrate and activated by 4.8 mmol/l LiCl. The latter result could be masking an inhibitory effect of acetoacetate. Chemotactic movements of neutrophils, as evaluated in a modified Boyden chamber using homologous zymosan-activated serum (ZAS) as a chemoattractant, were slightly but significantly reduced by a 2.4 mmolar concentration of the ketone bodies, administered singly or simultaneously, and by LiCl. We conclude therefore that the inhibitory effect of lithium-acetoacetate could be due to its lithium component. The 4.8 mmol/l dose of acetoacetate and beta-OH butyrate significantly decreased chemotaxis only when both compounds were added simultaneously. No effect of 4.8 mmol/l LiCl was observed. These results suggest that ketone bodies, in particular beta-OH butyrate, could directly influence particle uptake and chemotaxis in neutrophils. Although other factors could decrease the efficiency of the immune system in ketotic ruminants, the effects of the ketone bodies on neutrophils functions may explain the high frequency of infectious disease during 'ketotic syndrome'. The immunomodulatory effect of lithium needs to be evaluated further and it should be considered when testing lithium compounds.