HDFx and Methylated DNA; With Histones Upregulated in Macrophages/ Monocytes Derived From Animal Survivors Subjected to Traumatic, Endotoxin, and Hemorrhagic Shock: Importance of Epigenesis and Potential Reasons for Resistance to Bacterial, Fungal and Viral Infections

Each year approximately 60,000 people die from hemorrhagic shock in the U.S.A. with about two million deaths worldwide [1]. Deaths from traumatic shock, worldwide, has been difficult to estimate, due to battles/wars in many countries, but is thought to be more than two million victims/year [1]. Many reasons for these large numbers of deaths are known [for review, see1], for example, inadequate therapeutic measures, unavailability of adequate blood/ plasma/fluid replacement, seeing the patient too late, and unavailability of trained ER personnel, among the major reasons [for recent review, see1]. Another predominant reason for large numbers of hemorrhagic and traumatic shock deaths is the risk of sepsis in many of these victims, resulting in septic shock having mortalities in excess of 40- 75%, depending upon locality, with the lower numbers in the U.S.A. Lastly, and most important is “natural resistance of the body to infectious microorganisms” (i.e, bacteria, funguses, viruses, parasitic organisms, etc.). What is responsible for “natural resistance” has been studied for more than 150 years. We know that the “innate” and “adaptive” immune systems are key elements in defense against infectious microorganisms [2, 3]. But, which elements of these systems make-up major aspects of “resistance” and “host defense” still remains to be worked out. Using starfish, more than 140 years ago, the pioneer/father of immunology, and Nobel Laureate, Elie Metchnikoff, believed that white blood cells and macrophages were key to host-defense [4]. He also believed the body develops molecules/substances, which are key to resistance to infectious microorganisms [4].