Broad-spectrum chemokine inhibitors (BSCIs) and their anti-inflammatory effects in vivo.
Inappropriate inflammation is a component of a wide range of human diseases, including autoimmune disease, atherosclerosis, osteoporosis and Alzheimer's disease. Chemokines play an important role in orchestrating leukocyte recruitment during inflammation, and therefore represent an important target for anti-inflammatory therapies. Unfortunately, the chemokine system is complex, with about 50 ligands and 20 receptors, often acting with redundancy, making selection of appropriate specific antagonists difficult. One approach to overcoming this difficulty may be the development of broad-spectrum chemokine inhibitors (BSCIs). Here we review the present state of knowledge on BSCIs, including their activity in vitro and their anti-inflammatory effects in vivo, and discuss the future development of BSCIs as anti-inflammatory therapies for use in the clinic.
Grainger
David J
DJ
Department of Medicine, Cambridge University, Box 157, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. djg15@cam.ac.uk
Reckless
Jill
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D018925:Chemokines / Q000037:antagonists & inhibitors*; D017124:Conserved Sequence; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010881:Piperidones / Q000737:chemistry / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
C446054:3-(undec-10-enoylamino)glutarimide; D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D018925:Chemokines; D010455:Peptides; D010881:Piperidones