Novel agents in the therapy of endotoxic shock

Endotoxic shock, or Gram-negative septic shock, can occur as a component of Gram-negative sepsis and is characterised by hypotension, poor tissue perf usion and multi-organ dysfunction. Despite antibiotic therapy and intensive care management, the morbidity and mortality rates of Gram-negative septic shock remain high. Endotoxin mediates its effects through interaction with receptors on the surface of a variety of host cells. These interactions re sult in the production and release of numerous biochemical mediators includ ing nitric oxide, cytokines, prostaglandins and leukotrienes and toxic oxyg en radicals. It is these biochemical mediators that exert toxic effects dur ing endotoxic shock and which are often the target of novel treatment strat egies. Several of these pharmacological agents are currently being investig ated for use in Gram-negative septic shock and include inhibitors of the en zyme responsible for nitric oxide production, scavengers of the nitric oxid e molecule and cytokine modulators. Although many agents have been studied for potential use as modulators of cytokine levels, this study will focus o n pentoxifylline and the 21-aminosteroids, or lazaroids. Examination of the literature regarding pharmacological agents used to treat endotoxic shock often yields confusing and contradictory results. The reasons for these mix ed results include differences in models, drug dosages, dosing methods and intervals and timing of administration relative to disease duration and sev erity. However, despite mixed results, several of the drugs discussed in th is paper offer promise in the therapy of an often frustrating and lethal co ndition.