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Şifremi Unuttum

İmmün Stimülasyon: Septik Şok Tedavisinde Kullanılabilir mi?


EMBARGOED UNTIL: Wednesday, September 11, 8:30 AM MDT

(Session 55, Paper B-390)

Steven Opal
Alpert Med. Sch. of Brown Univ., Providence, RI, United States


Phone: (401) 729-2545

Attempts to improve the outcome of patients with septic shock with anti-inflammatory agents have generally been unsuccessful.  There are numerous potential reasons for these failures but most prominent among them is evidence of marked immune suppression in many critically ill patients with sepsis. Experiments in animal models and clinical experience indicate that targeting the immune system during the course of severe infection is a complex and potentially hazardous process.  The host with a severe infection has to clear the microbial pathogen; at the same time the host must regulate the extent of immune activation to prevent collateral damage to normal tissue as a result of the inflammatory process around sites of tissue infection.  Techniques to monitor the systemic inflammatory state of patients with severe infection are now becoming available.  Treatments are needed to improve the outcome in septic shock independent from standard therapy such as antibiotics and fluids.  Immune regulatory therapies will be tailored to each patient in an effort to return their immune status to a normal state.  This should improve outcome and prevent the long term, injurious effects of acute severe inflammation.  Sepsis can result in residual loss of function, mobility and impaired memory function in survivors for several years after apparent recovery from sepsis.

In experimental studies and in recent clinical investigations, it is becoming increasingly evident that an acquired form of relative immune suppression is a frequent event following severe infection.  This immune dysregulation can disrupt appropriate clearance of microbial pathogens and may increase the risk of health care-associated infections.  The onset of sepsis-induced immune suppression may occur rapidly in systemic inflammatory states, particularly in elderly patients, immunocompromised patients, and in seriously ill patients who become infected after prolonged ICU stays.  A type of immune exhaustion develops during periods of marked infection-induced, antigen excess akin to the immune consequences seen in advanced malignancy. Sepsis-induced immune suppression is readily demonstrable by studying cellular T cell immune function, and is often manifest by secondary infections by opportunistic microorganisms usually encountered only in severely immunocompromised patients.  Multiple treatment options might afford protection from the adverse consequences of sepsis-induced immune suppression.  Augmentation of existing host responses by T cell adjuvants such as Interleukin -7, or IL-15 or thymic growth factors is a possible therapy, or antibodies that target co-inhibitory molecules such as programed death 1 (PD1) or B and T cell lymphocyte attenuator (BTLA).  Immune stimulants including granulocyte-macrophage colony stimulating factor or gamma interferon are in clinical trials at present for selected populations at risk for sepsis-related immune suppression.

Such treatment strategies can only be used with safety and selectivity if the technology is available to rapidly assess immune function in acutely ill patients.  Such techniques as immune screening during sepsis for cell markers on immune effector cells are now becoming available, along with measurements of circulating biomarker molecules indicative of relative immune suppression.  It is hoped that this new way of viewing sepsis might improve the outcome in these vulnerable patients who continue to suffer considerable morbidity and mortality as a result of systemic infectious diseases.