Καθοριστικές ανοσολογικές διαταραχές κατά τη μετάπτωση πολυτραυματία σε βακτηριακή σήψη: πειραματική μελέτη ; Decisive immunological changes during transition of multiple trauma to bacterial sepsis: experimental evidence

Sepsis develops when well-conserved structures of microorganisms(also known as pathogen-associated molecularpatterns, PAMPs) bind to transmembrane or intracellularreceptors of the innate immune system and particularly toblood monocytes and tissue macrophages. This bindingleads to the release of pro-inflammatory and antiinflammatorycytokines which induce clinical sepsis. Themost widely studied PAMP is endotoxin (lipopolysaccharide,LPS) of the cell wall of Gram-negative bacteria whichbinds to the transmembrane Toll-like receptor (TLR-4) onmonocytes and macrophages. Exposure to bacterial LPScauses monocytes and macrophages to become tolerantshowing decreased cytokine production upon LPS reexposure. Multiple traumas are a major cause of death of patientshospitalized in Intensive Care Units (ICU). Patients usuallypresent with systemic inflammatory response of nonbacterialetiology at their initial admission to the ICU. Patientssurviving this post-traumatic response often developsepsis as a consequence of bacterial superinfection. Theinitial post-traumatic systemic inflammatory response iscaused by the stimulation of leukocytes to release inflammatorymediators during binding of endogenous ligandsreleased after injury to the TLRs. Examples of such componentsare uric acid, mitochondrial DNA and non-histone nuclearproteins known as “alarmins” or danger-associatedmolecular patterns (DAMPs). In analogy to the phenomenon of tolerance to bacterialLPS, it would be expected that the innate immune cells ofthe trauma patients manifest tolerance to alarmins andconsequently would release less cytokines after reexposureto bacterial PAMPs. If this hypothesis holdstrue, patients bearing multiple traumas when theydevelop severe sepsis may have a relatively betterprognosis compared to patients without prior multipletraumas as the predisposing factor for severe sepsis. Onthe other hand, long-term depression of immune responsesafter multiple traumas could also be associatedwith increased susceptibility to opportunistic infections.This ...