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J Chemother. 1999 Dec;11(6):536-40.

Sepsis and septic shock: pro-inflammatory or anti-inflammatory state?

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Dept. of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma, Italy.


A considerable body of evidence indicates that together with an important pro-inflammatory reaction, a anti-inflammatory response contributes to the onset of sepsis and organ failure. At a local site of injury or infection and during the initial appearance of pro- and anti-inflammatory mediators in the circulation, the beneficial effects of these compounds counterbalance their harmful effects. Only when the balance between these two forces is lost may these substances become harmful. The sequelae of an unbalanced systemic inflammatory reaction include derangement of microcirculation, shock, transudation into organs and defects of coagulation. An unbalanced systemic compensatory anti-inflammatory response often results in anergy and immunosuppression. The pro-inflammatory and anti-inflammatory conditions may ultimately reinforce each other, creating a state of destructive immunologic dissonance. In the present report, recent literature on cytokines was reviewed together with the 89 clinical papers published between 1993 and 1997 on the role of cytokines during sepsis and other inflammatory reactions. Cytokines were analyzed in more than 5,000 patients. Sepsis and septic shock were the two groups most represented (2834 individuals and 550 respectively). Only 12% (11) of the studies showed a correlation with the presence of sepsis or septic complications. Overall 27 (39%) studies found a correlation between levels of cytokine and mortality. Fifty (62%) of the 80 studies that investigated this correlation found that the amount of cytokines did not predict death. The rest of the 30 (48%) investigations depicted an unhomogeneous picture: even though 27 studies evidenced higher levels of cytokines in non-survivors, 3 studies found the opposite.

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