? Patients with sepsis are characterized by defects in both the innate and adaptive immune system. During sepsis there is an extensive apoptosis induced loss of lymphocytes that has highly negative consequences on the host's immune competence. Apoptosis of lymphocytes not only results in depletion of key helper and effector lymphocytes but also results in an impaired innate immune response because of the intimate feedback or 'cross-talk' between the innate and adaptive immune systems. ? Furthermore, apoptotic lymphocytes are engulfed by macrophages and dendritic cells and this process results in immune suppression or apoptosis in these scavenger cells as well. Given the above, it is not surprising that numerous laboratories have demonstrated using a variety of strategies that prevention of lymphocyte death can improve sepsis survival. This is the focus of the current application. ? An important finding in research investigating the life and death of lymphocytes is the critical role of accessory stimuli in determining cell fate. Once a B or T cell has been activated, many factors are involved in the cell's decision to undergo proliferation or apoptosis. In this proposal, selected molecules that have anti-apoptotic activity in lymphocytes will be administered to determine if sepsis induced lymphocyte apoptosis can be ameliorated. Effects of anti-apoptotic therapy on cytokine profiles and survival in a clinically relevant murine sepsis model will be evaluated. ? ?
| Francois, Bruno; Jeannet, Robin; Daix, Thomas et al. (2018) Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight 3: |
| Drewry, Anne M; Fuller, Brian M; Skrupky, Lee P et al. (2015) The presence of hypothermia within 24 hours of sepsis diagnosis predicts persistent lymphopenia. Crit Care Med 43:1165-9 |
| Drewry, Anne M; Hotchkiss, Richard S (2015) Sepsis: Revising definitions of sepsis. Nat Rev Nephrol 11:326-8 |
| Hutchins, Noelle A; Unsinger, Jacqueline; Hotchkiss, Richard S et al. (2014) The new normal: immunomodulatory agents against sepsis immune suppression. Trends Mol Med 20:224-33 |
| Fuller, Brian M; Mohr, Nicholas M; Hotchkiss, Richard S et al. (2014) Reducing the burden of acute respiratory distress syndrome: the case for early intervention and the potential role of the emergency department. Shock 41:378-87 |
| Walton, Andrew H; Muenzer, Jared T; Rasche, David et al. (2014) Reactivation of multiple viruses in patients with sepsis. PLoS One 9:e98819 |
| Drewry, Anne M; Samra, Navdeep; Skrupky, Lee P et al. (2014) Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock 42:383-91 |
| Hotchkiss, Richard S; Monneret, Guillaume; Payen, Didier (2013) Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol 13:862-74 |
| Drewry, Anne M; Fuller, Brian M; Bailey, Thomas C et al. (2013) Body temperature patterns as a predictor of hospital-acquired sepsis in afebrile adult intensive care unit patients: a case-control study. Crit Care 17:R200 |
| Takasu, Osamu; Gaut, Joseph P; Watanabe, Eizo et al. (2013) Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med 187:509-17 |
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