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Departments of
* Surgery and
Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida 32610, USA
1Correspondence: Department of Surgery, University of Florida College of Medicine, Room 6116, Shands Hospital, 1600 S.W. Archer Rd., PO Box 100286, Gainesville, FL 32610-0286, USA. E-mail: moldawer{at}surgery.ufl.edu
The treatment of sepsis and septic shock remains a clinical conundrum,
and recent prospective trials with biological response modifiers aimed
at the inflammatory response have shown only modest clinical benefit.
Recently, interest has shifted toward therapies aimed at reversing the
accompanying periods of immune suppression. Studies in experimental
animals and critically ill patients have demonstrated that increased
apoptosis of lymphoid organs and some parenchymal tissues contributes
to this immune suppression, anergy, and organ system dysfunction.
During sepsis syndromes, lymphocyte apoptosis can be triggered by the
absence of IL-2 or by the release of glucocorticoids, granzymes, or the
so-called ‘death’ cytokines: tumor necrosis factor 
or Fas ligand.
Apoptosis proceeds via auto-activation of cytosolic and/or
mitochondrial caspases, which can be influenced by the pro- and
anti-apoptotic members of the Bcl-2 family. In experimental animals,
not only can treatment with inhibitors of apoptosis prevent lymphoid
cell apoptosis; it may also improve outcome. Although clinical trials
with anti-apoptotic agents remain distant due in large part to
technical difficulties associated with their administration and tissue
targeting, inhibition of lymphocyte apoptosis represents an attractive
therapeutic target for the septic patient.—Oberholzer, C., Oberholzer,
A., Clare-Salzler, M., Moldawer, L. L. Apoptosis in sepsis: a new
target for therapeutic exploration.
Key Words: Bcl-2 • caspases • lymphocytes • neutrophils
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C. Oberholzer, A. Oberholzer, F. R. Bahjat, R. M. Minter, C. L. Tannahill, A. Abouhamze, D. LaFace, B. Hutchins, M. J. Clare-Salzler, and L. L. Moldawer Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis PNAS, September 25, 2001; 98(20): 11503 - 11508. [Abstract] [Full Text] [PDF]
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