Immunology of Septic Shock Clinical Trial
Official title:
Evaluation of Immunosuppression in Septic Shock: Biomarkers and Pharmacological Restoration (IMMUNOSEPSIS)
Septic syndromes (systemic inflammatory response associated with infection) remain a major
although largely under-recognized health care problem and represent the first cause of
mortality in intensive care units. While it has long been known that sepsis deeply perturbs
immune homeostasis by inducing a tremendous systemic inflammatory response, novel findings
indicate that sepsis indeed initiates a more complex immunologic response that varies over
time, with the concomitant occurrence of both pro- and anti-inflammatory mechanisms. As a
resultant, after a short pro-inflammatory phase, septic patients enter a stage of protracted
immunosuppression. This is illustrated in those patients by reactivation of dormant viruses
(CMV or HSV) or infections due to pathogens, including fungi, which are normally pathogenic
solely in immunocompromised hosts. These alterations might be directly responsible for
worsening outcome in patients who survived initial resuscitation as nearly all immune
functions are deeply compromised. Both arms of immunity (innate and adaptive) are indeed
markedly suppressed (including enhanced leukocyte apoptosis, lymphocyte anergy and
deactivated monocyte functions). New promising therapeutic avenues are currently emerging
from those recent findings such as adjunctive immunostimulation for the most
immunosuppressed patients. The prerequisite for immunostimulation administration (IFNg,
GM-CSF, IL-7) however relies on the investigators capacity in identifying the patients who
could benefit from it, as there is no clinical sign of immune dysfunctions. The main
objectives are:
1. to identify the best biomarkers for sepsis-induced immunosuppression and
2. to evaluate ex vivo whether drugs could rejuvenate immune functions.
n/a
Observational Model: Cohort, Time Perspective: Prospective