With the discovery almost 25 years ago that administration of tumor necrosis factor-α could
produce shock and tissue injury similar to severe sepsis, the fundamental role for cytokines
in experimental sepsis was established (1, 2) The dramatic improvement in survival, first
seen in mice and then confirmed in primates with bacteremic shock, produced simply by
inhibiting a single cytokine (3, 4), resulted in unbridled optimism that sepsis mortality in
hospitalized patients could be dramatically reduced. This outlook pervaded the collective …