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(Chest. 2003;123:451S-459S.)
© 2003 American College of Chest Physicians

The Problems and Challenges of Immunotherapy in Sepsis*

Stanley A. Nasraway, MD, FCCP

* From the Department of Surgery and Section of Critical Care Research, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA.

Correspondence to: Stanley A. Nasraway, MD, FCCP, Department of Surgery, Tufts-New England Medical Center, 750 Washington St, Box 4630, Boston, MA 02111; e-mail: Snasraway{at}lifespan.org

Despite decades of research, the morbidity and mortality of sepsis and septic shock remain very high. To further compound the problem, results from all investigative trials (with one exception) have shown that tested immunotherapies aimed at modulating the excessive expression of key cytokines, such as the interleukins and tumor necrosis factor, have been either equivalent or inferior to placebo. While controversy prevails in terms of continuing such investigative trials, study designs can be held accountable for inherent flaws. Testing for the wrong hypothesis, errant study design, using the wrong agent, focusing on an inappropriate target group, excessive expectations, and uncontrolled variables have potentially obscured the real efficacy such agents might have to offer. By standardizing protocols and reducing uncontrolled variables, research can be more precisely targeted so as to unmask the real benefits to the patient.

Key Words: cytokines • immunomodulators • sepsis • sepsis trials • septic shock




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