Figure 1.

Perinatal diet may influence glucocorticoid negative feedback following immune challenge. (A) Pathogens such as lipopolysaccharide act at toll-like receptors (e.g., TLR4) on immune cells leading to phosphorylation of inhibitory factor (I)κ B, releasing nuclear factor (NF)κ B from its complex and allowing it to be translocated to the nucleus. NKκ B is responsible for the transcription of pro- and anti-inflammatory cytokines, the former of which stimulate the cyclo-oxygenase 2-mediated conversion of aracidonic acid into prostaglandins. Prostaglandins (e.g., PGE2) act at the brain to stimulate fever and sickness behavior and recruit the HPA axis. Once released, glucocorticoids (GC) negatively feed back to inhibit further NFκ B-mediated transcription of cytokines. (B) The perinatal diet may influence glucocorticoid negative feedback by altering expression of glucocorticoid receptors (GR) in the hippocampus and hypothalamus leading to less efficient glucocorticoid-mediated inhibition of NFκ B and an exacerbated immune response.