Macrophages play a central role in the host response to
injury, infection and sepsis. Macrophage activities include
antigen presentation, chemotaxis, phagocytosis, bactericidal
activity, cytokine secretion and wound repair. Glucose is
the primary metabolic substrate for the macrophage and
effi cient glucose infl ux is essential for optimal
macrophage function. Macrophages and neutrophils
require NADPH for the formation of the reactive oxygen
species, nitric oxide and superoxide as well as many
biosynthetic pathways. Metabolism of glucose via the
pentose pathway provides the metabolic intermediates
required for the generation of NADPH. Following
thermal injures, trauma and sepsis, non-insulin mediated
glucose uptake is increased. Th e majority of the increased
glucose uptake occurs in macrophage rich tissues [26,27].
Th ese data suggest that the increased energy requirements
of activated macrophages and neutrophils during
infection and tissue injury are regulated by enhanced
cellular glucose uptake related to the increased glucose
diff usion gradient and increased expression of glucose
transporters. In addition, these mechanisms ensure
adequate glucose uptake by neuronal tissue in the face of
decreased microvascular fl ow. Iatrogenic normalization
of blood glucose may therefore impair immune and
cerebral function at a time of crises. Indeed, two
independent groups of investigators using microdialysis
and brain pyruvate/lactate ratios demonstrated that
attempts at blood glucose normalization in critically ill
patients with brain injury were associated with a greater
risk of critical reductions in brain glucose levels and brain