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Corticotropin Releasing Hormone (CRH) and Innate Immune responses to Gram negative Bacteria

Final Activity Report Summary - CRH AND INNATE IMMUNITY (Corticotropin Releasing Hormone (CRH) and Innate Immune responses to Gram negative Bacteria)

All organisms are faced with a variety of challenges from the external environment that are collectively referred as stressors. The response to these stressors constitutes an adaptive mechanism coordinated by a component of the endocrine system, the hypothalamic-pituitray-adrenal (HPA) axis. This system includes a part in the central nervous system that secretes two hormones Corticotropin-releasing hormone (CRH) and adrenocorticotropin hormone (ACTH), and a component in the body, the adrenal glands, that release glucocorticoid.

One of the major stressors for the organism is its challenge by pathogenic organisms that can cause infection and inflammation. The organism recognizes its invasion by the different organisms via specific families of receptors including Toll-like receptors (TLRs), that when activated by a pathogen initiate a series of events that ends with the production by the organism of factors termed cytokines that are involved in the development of further disease. It has been described by a variety of investigators that pathogens activate the stress response, shown by increased levels of glucocorticoid in the blood.

In this study we evaluated the hypothesis that HPA axis and the cascade of activation of TLR4, a receptor that recognizes a big family of harmful bacteria, the Gram negative, interact to coordinate the response to these organisms. In addition, we evaluated the exact level(s) of their interaction at the cellular level. We believe that characterisation of the molecular mechanisms of interaction of these systems will provide new insights in the development of specific therapeutic regimens for this serious group of infections that can often result in the development of endotoxemia and sepsis.