Targeting inflammatory diseases via apoptotic mechanisms.
Induction of apoptosis in immune cells is a crucial mechanism used by the body to produce immune resolution. The homeostatic mechanisms employed are currently being identified and, to date, studies have highlighted some of the signals that regulate the immune response. The exposure of phosphatidylserine on the surface of an apoptotic neutrophil is sufficient to limit the immune response in acute inflammation, whereas apoptosis of key effector cells can limit the response in chronic inflammation. Other therapeutic approaches that are being investigated include the inhibition of apoptosis by blocking the caspase cascade. This approach will be of particular relevance for the treatment of inflammatory central nervous system diseases and sepsis. An alternative approach being examined is forced resolution, whereby apoptosis is induced in effector cells, principally T cells, through activation-induced cell death mediated by Fas receptors. Inhibitors of this mechanism have been identified and targeted in several studies.
Murphy
Finbarr J
FJ
Eirx Therapeutics Ltd, 2800 Cork Airport Business Park, Kinsale Road, Cork, Ireland. fmurphy@eirx.com
Hayes
Ian
I
Cotter
Thomas G
TG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism / Q000502:physiology; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D008214:Lymphocytes / Q000201:enzymology / Q000473:pathology / Q000502:physiology; D018805:Sepsis / Q000201:enzymology / Q000276:immunology / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D020169:Caspases