Problems with Magic Bullets: Future Trials and Multiagent Therapy

  • Arthur E. Baue


The explosion of knowledge about mediators of inflammation, injury, and infection has been impressive. These topics are described in other chapters in this book and are summarized in Table 57.1. Antagonists to all of these substances have been produced as monoclonal antibodies, receptor antagonists, or other enzymes or blocking agents; and many have been tried clinically. Many of these agents and the clinical trials have been reviewed by Neugebauer et al.2 The frequency of infection, sepsis, injury, or inflammation in producing multiple organ failure led to clinical trials of these so-called magic bullets for the treatment of patients with sepsis and after injury. These trials have had limited success or negative results, despite considerable evidence of the efficacy or protection by such agents in experimental animals and in studies of human volunteers. I believe the major reasons for these negative results have been (1) the use of general entry criteria for the trials rather than the treatment of specific diseases or injuries and (2) the redundancy and overlap of these complex, interacting substances. Thus the “magic bullet” approach has failed because it oversimplifies a complex biologic system.3


Nitric Oxide Septic Shock Systemic Inflammatory Response Syndrome Acute Respiratory Distress Syndrome Multiple Organ Failure 
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© Springer Science+Business Media New York 2000

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  • Arthur E. Baue

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