Linked Life Data

12441145

Source:http://linkedlifedata.com/resource/pubmed/id/12441145

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-11-20
pubmed:abstractText
Recombinant human interleukin (IL)-18 (rHuIL-18) has a potential as a therapeutic agent in cancer and is currently in drug development. Since human IL-18 displays 96% and 100% amino acid sequence homology with cynomolgus monkey and chimpanzee IL-18, respectively, the biological responses to rHuIL-18 were evaluated in these species. A single intravenous dose of rHuIL-18 at 1 or 10mg/kg in cymonolgus monkeys caused a transient reduction in lymphocyte counts, induction of IL-1alpha and tumour necrosis factor alpha (TNF-alpha) mRNA in whole blood cells and a marked increase in plasma neopterin. rHuIL-18 administered to cynomolgus monkeys at doses of 0.3 or 3mg/kg for two 5-day cycles (Days 1-5 and 15-19) resulted in increased monocyte counts, induction of NK cells and concomitant increases in plasma IL-12 and neopterin. Administration of repeat doses of rHuIL-18 at 10mg/kg to chimpanzees was associated with increased monocyte counts, upregulation of FcgammaRI surface expression on monocytes, and increased IL-8, IL-12 and neopterin in plasma. These studies demonstrate, for the first time, the immunostimulatory activity of rHuIL-18 in vivo. The described pharmacological profile of rHuIL-18 in both cynomolgus monkeys and chimpanzees is indicative of the immunotherapeutic potential of rHuIL-18 in the treatment of cancer.
pubmed:language
eng
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:author
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38-48
pubmed:dateRevised
2004-11-17
pubmed:articleTitle
Immunopharmacology of recombinant human interleukin-18 in non-human primates.
pubmed:affiliation
Department of Safety Assessment, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, PO Box 1539, King of Prussia, PA 19406, USA. danuta.j.herzyk@gsk.com