In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.Anyone who has experienced a viral or bacterial infection knows what it means to feel sick. The behaviour of sick people changes dramatically; they often feel feverish and nauseated, ignore food and beverages, and lose interest in their physical and social environments. They tire easily and their sleep is often fragmented. In addition, they feel depressed and irritable, and can experience mild cognitive disorders ranging from impaired attention to difficulties in remembering recent events. Despite their negative impact on well-being, these symptoms of sickness are usually ignored. They are viewed as uncomfortable but banal components of infections 1 .Sickness is a normal response to infection, just as fear is normal in the face of a predator. It is characterized by endocrine, autonomic and behavioural changes and is triggered by soluble mediators that are produced at the site of infection by activated accessory immune cells. These mediators are known as pro-inflammatory cytokines, and include interleukin-1α and β (IL-1α and IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). They coordinate the local and systemic inflammatory response to microbial pathogens. However, NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript these peripherally produced cytokines also act on the brain to cause the aforementioned behavioural symptoms of sickness. Recently, it has been suggested that 'sickness behaviour' 2, 3, a term used to describe the drastic changes in subjective experience and behaviour that occur in physically ill patients and animals, is an expression of a previously unrecognized motivational state. It is responsible for re-organizing perceptions and actions to enable ill individuals to cope better with an infection4.During the last five years, it has been established that pro-inflammatory cytokines induce not only symptoms of sickness, but also true major depressive disorders in physically ill patients with no previous history of mental disorders. Some of the mechanisms that might be responsible for inflammation-mediated sickness and depression have now been elucidated. These findings suggest that the brain-cytokine system, which is in essence a diffuse system, is the unsuspected conductor of the ensemble of neuronal circuits and neurotransmitters that organize physiologi...

Acute cognitive disorders are common in elderly patients with peripheral infections but it is not clear why. Here we injected old and young mice with Escherichia coli lipopolysaccharide (LPS) to mimic an acute peripheral infection and separated the hippocampal neuronal cell layers from the surrounding hippocampal tissue by laser capture microdissection and measured mRNA for several inflammatory cytokines (IL-1β, IL-6, and TNFα) that are known to disrupt cognition. The results showed that old mice had an increased inflammatory response in the hippocampus after LPS compared to younger cohorts. Immunohistochemistry further showed more microglial cells in the hippocampus of old mice compared to young adults, and that more IL-1β-positive cells were present in the dentate gyrus and in the CA1, CA2 and CA3 regions of LPS-treated old mice compared to young adults. In a test of cognition that required animals to effectively integrate new information with a preexisting schema to complete a spatial task, we found that hippocampal processing is more easily disrupted in old animals than in younger ones when the peripheral innate immune system is stimulated. Collectively, the results suggest that aging can facilitate neurobehavioral complications associated with peripheral infections probably by allowing the over expression of inflammatory cytokines in brain areas that mediate cognitive processing.

Dietary fiber (DF) is deemed to be a key component in healthy eating. DF is not a static collection of undigestible plant materials that pass untouched or unencumbered through the gastrointestinal (GI) tract; instead, DFs are a vast array of complex saccharide-based molecules that can bind potential nutrients and nutrient precursors to prevent their absorption. Some DFs are fermentable, and the GI tract catabolism leads to the generation of various bioactive materials, such as short-chain fatty acids (SCFAs), that can markedly augment the GI tract biomass and change the composition of the GI tract flora. The health benefits of DFs include the prevention and mitigation of type 2 diabetes, cardiovascular disease and colon cancer. By modulating food ingestion, digestion, absorption and metabolism, DFs reduce the risk of hyperlipidemia, hypercholesterolemia and hyperglycemia. Emerging research has begun to investigate the role of DFs in immunomodulation. If substantiated, DFs could facilitate many biologic processes, including infection prevention and the improvement of mood and memory. This review describes the accepted physiologic functions of DFs and explores their new potential immune-based actions.