The Pro-Inflammatory Cytokine Cascade

Part of the Update in Intensive Care Medicine book series (volume 31)


The production of pro-inflammatory cytokines is a prerequisite for initiating the anti-infectious process, whereas their exacerbated production during severe inflammation may contribute to deleterious consequences. The capacity of interleukin (IL)-l and tumor necrosis factor-alpha (TNF-a) to induce inflammatory mediators contributes to their pro-inflammatory properties. Phospholipase, cyclooxygenase and lipoxygenase are activated by IL-1 and TNF-a leading to the release of prostaglandins, thromboxane, leukotrienes, and platelet activating factor (PAF). Free radicals (superoxide [O 2 ], nitric oxide [NO]), and proteolytic enzymes are other mediators produced by target cells in response to IL-1 and TNF-a. Other cytokines, including chemokines such as IL-8 or some T-cell derived cytokines, such as lymphotoxin-α are also involved in the cytokine cascade (Fig. 1). Different experimental approaches have demonstrated the contribution of the pro-inflammatory cytokines to the harmful effects observed in sepsis, trauma, burns, hemorrhage, severe surgery and other pathophysiological situations leading to systemic inflammatory response syndrome (SIRS). The injection of recombinant pro-inflammatory cytokines mimics some of the clinical parameters observed in SIRS patients and the use of anti-cytokine antibodies prevents most of the deleterious effects observed in animal models of SIRS.
Fig. 1.

Schematic representation of the pro-inflammatory cytokine cascade


Proinflammatory Cytokine Systemic Inflammatory Response Syndrome Acute Phase Protein Multiple Organ Dysfunction Syndrome Endotoxic Shock 
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© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  1. 1.Institut PasteurUnité d’Immuno-AllergieParisFrance

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