Submitted to: Microscopy Research and Technique
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 20, 2001
Publication Date: April 1, 2002
Citation: Microscopy Research & Technique 57:120-129, 2002.
Interpretive Summary: Adrenomedullin is a rather newly discovered hormone with biological properties that span the areas of growth, differentiation, regulation of metabolism, and restoration of normal functions in the body after an immunological event that challenges health. Adrenomedullin plays a significant role in how the body handles the inflammatory response to immune challenge. Functions include redirecting blood flow and maintainin tissue oxygenation, redirecting metabolism through effects on the regulation of hormone secretion from the pancreas, and defending against breakages in a cell's genetic material the DNA. The major functions of adrenomedullin are carried out where the tissue needs to react to the immune challenge. Although major changes in the plasma concentration of the hormone accompany the onset of inflammation, the functions of the increased plasma concentrations are not known. Adrenomedullin may be considered also a marker for immune stress where detection of increased concentrations of the hormone may signal a need for a physician or veterinarian to check further for the presence of infection.
The upregulation of adrenomedullin (AM) gene expression and increases in systemic circulatory as well as localized tissue AM concentrations is well coordinated to the onset and progression of trauma, infection, and sepsis. By clinical definition, the process of inflammation constitutes an orchestrated cascade of localized tissue and systemic responses to immunological challenges. Classical responses to the onset of disease stresses are manifested in the timely elaboration of humoral, blood-born signal effectors (such as adrenocortical and locally produced tissue hormones, immune cytokines, and inorganic signals such as nitric oxide) as well as patterned migration and infiltration of circulating bone marrow- derived cells (mononuclear cells such as monocyte-macrophages and polymorphonuclear cells like neutrophils) largely associated with or delivered through the vascular system. Athrosclerosis, diabetes, and cardiovascular disease, as well as nutritional metabolic derangements and persistent subclinical infection, perturb the regulatory feedback loops necessary for proper control of response effectors like hormones and cytokines. In essence the inflammatory response can be thought of in three phases: a period of severity assessment, a period of remediation, and a period of homeostatic restoration. Indeed, AM has differential effects on cellular metabolism, immune function, endocrine function, and cardiovascular function. This peptide appears to play a pivotal role in both reprioritizing the biological needs of tissues and organs during the three phases of inflammatory response as well as a role in restoring homeostatic equilibrium to the body.