The Pathogenesis of Sepsis: “If We Cannot beat them Alone Join Them?”

Abstract

Sepsis and septic shock are probably the least understood human disorders which worldwide take the lives of millions of patients. Sepsis may be defined as a multifactorial synergistic phenomenon where no unique damageassociated molecular patterns –alarming is identified which if successfully neutralized, might mitigate and protects against death in sepsis. Microorganisms which invade the blood stream may activate neutrophils to adhere to endothelial cells and to form oxidant – dependent nets rich in highly toxic nuclear histones claimed to be the main cause of death in sepsis due to the dysregulation of endothelial functions. However, the histone saga was recently critically debated since high levels circulating histones are also found in many clinical disorders unrelated to sepsis, therefore, histones may not be considered as a unique damage-associated molecular patternsalarming but as additional markers of severe cell damage. We hereby argue that the main cause of tissue damage in sepsis may be an end result of a synergism between the numerous neutrophils pro inflammatory agents and the multiplicity of similar pro inflammatory agents generated by hemolytic steptoccocci and by additional pathogenic microorganism which recruit large numbers PMNs to the inflammatory sites. It is recommended that in sepsis caused by hemolytic streptococci and by additional toxigenic bacteria, a use of cocktails of antagonists might be more beneficial therapeutic strategies and this in view of the total failure to treat sepsis only by administrations of single antagonists. Also, targeting PMNs by immunological strategies should be sought for, to mitigate synergies between leukocytes and microbial cells.