Heparin in inflammation: potential therapeutic applications beyond anticoagulation.
In this chapter we have described anti-inflammatory functions of heparin distinct from its traditional anticoagulant activity. We have presented in vivo data showing heparin's beneficial effects in various preclinical models of inflammatory disease as well as discussed some clinical studies showing that the anti-inflammatory activities of heparin may translate into therapeutic uses. In vivo models that use low-anticoagulant heparins indicate that the anticoagulant activity can be distinguished from heparin's anti-inflammatory properties. In certain cases such as hypovolemic shock, the efficacy of a low-anticoagulant heparin derivative (GM1892) exceeds heparin. Data also suggest that nonconventional delivery of heparin, specifically via inhalation, has therapeutic potential in improving drug pharmacokinetics (as determined by measuring blood coagulation parameters) and in reducing the persistent concerns of systemic hemorrhagic complications. Results from larger clinical trials with heparin and LMW heparins are eagerly anticipated and will allow us to assess our predictions on the effectiveness of this drug class to treat a variety of human inflammatory diseases.
Tyrrell
D J
DJ
Glycomed Incorporated, Alameda, California 94501, USA.
Horne
A P
AP
Holme
K R
KR
Preuss
J M
JM
Page
C P
CP
D000544:Alzheimer Disease / Q000188:drug therapy; D001249:Asthma / Q000188:drug therapy; D003093:Colitis, Ulcerative / Q000188:drug therapy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D006493:Heparin / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D016023:Integrins / Q000502:physiology; D007962:Leukocytes / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy; D012128:Respiratory Distress Syndrome / Q000188:drug therapy; D019087:Selectins / Q000378:metabolism; D012769:Shock / Q000188:drug therapy
D016023:Integrins; D019087:Selectins; D006493:Heparin