CRH Regulates On The Secretion Of Cytokines Of Abdominal Macrophage

Corticotropin-releasing hormone (CRH), involves in many physiological processes of brain, adrenad, gonad and placenta, etc, is one of the most important neurohormone and regulator of hypothalamic-pituitary-adrenal (HPA) AXIS. It has regulational ructions to endocrine , spontaneous, behavioral responses and direct influence on immunological function recently has been discovered. CRH's main receptors are CRH-R1 and CRH-R2, which are distributed in the spleen, heart, skin and myometrium except for the center. Moreover, on the macrophage of the spleen, we also have found them. But, the research of CRH-R's distribution and function on the lung, liver and kidney are scarcely reported until now. It is not clear macrophage, which are located at the end of the neuroendocrine immune system whether have been regulated by neuroendocrine immune system through CRH on the surface of cells.So, the subject will have research on the following aspects by the means of the severe trauma modal and macrophage culture in vitro: (1) Observing the changing pattern of CRH-R1 and CRH-R2 receptors' distributions and contents in the lung, liver, spleen, kidney and adrenal. (2)Observing the function and influence of CRH on abdominal macrophage's secreting cytokines such as TNF-a, IL-2, IL-6, IL-10 etc, further the effect of CRH's relationship with the expressed motive change of CRH-R, P-PKA and P-CREB of macrophage. The above two points have discussed the functions of CRH and intend to reveal the functions and significance of CRH in the process of synthetic response of outside neuroendocrine immunological regulation after severe trauma.The results and conclusions:1. There are CRH-R 1 and CRH-R2 receptors in liver, spleen, kidney, lung and adrenal. These two receptors are distributed on the endothelial cells andmacrophages of these organs, except the hepatocytes have CRH-R1 in liver. After severe traumatized, the content of CRH's receptors distributed the outside organizations have respectively increased significantly, as those in the lung are most outstanding. It suggests the outside organizations can directly involve in the process of neuroendocrine immunological regulation through the interaction of CRH and its receptors CRH-R1 and CRH-R2.2. CRH can induce abdominal cavity macrophage to produce and secrete cytokines, such as TNF-a, IL-6, IL-10 ECT. The increase of proinfiammatory cytokine, TNF-a's secretion is early and lasts for a relatively long time. But anti-inflammatory cytokine IL-10's increase is rather late and lasts for a relatively short period. All this reveals that CRH participates in the process of the immune regulation of outside macrophage, further perhaps participates in the regulation to body's immunologic balance.3. CRH-R1 and CRH-R2 receptors on the surface of the macrophage have participated in the Process of regulation function to outside macrophage.4. PKA, cAMP and CREB, these signal transduction molecules are related to CRH's regulated function on the cytokines' secretion of macrophage. But its mechanism needs some deep research.