Granulocytes as mediators of tissue injury in shock: therapeutic implications.
In summary, over the last twenty years, we have gained a substantially improved understanding of the ways in which granulocytes can damage host tissues. Most recently, there has been a great deal of interest in the intravascular behavior of granulocytes, and the possibility that such behavior might contribute to complications of extracorporeal circulations, bacteremic infections and shock. These insights give us several ideas about possible therapeutic interventions: corticosteroids or other drugs might be used to blunt granulocyte responsiveness; iron chelation might be used to limit the production of toxic hydroxyl radical; competitive inhibition of oxidant damage might be possible using such simple compounds as methionine; protease inhibitors might blunt endothelial cell delamination. Unfortunately, most of these therapies have been tried, with mixed results. It is likely that in most cases of shock, the damage worked by granulocytes occurs very early, often before the patient is recognized as having shock or being at risk for shock. Therefore, by the time a decision is made to employ one of the above modalities, it may already be too late. Perhaps the greatest opportunities for improving our ability to treat irreversible shock and the shock lung syndrome lie with the early identification of patients at risk for development of the syndrome, so that antigranulocyte therapies can be applied before the damage is done.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D010587:Phagocytosis; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D012769:Shock / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*
D000305:Adrenal Cortex Hormones