Immunopharmacology of recombinant human interleukin-18 in non-human primates. Export

@article{citeulike:6071936, abstract = {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.}, author = {Herzyk, Danuta J. and Soos, Jeanne M. and Maier, Curtis C. and Gore, Elizabeth R. and Narayanan, Padma K. and Nadwodny, Kimberly L. and Liu, Susan and Jonak, Zdenka L. and Bugelski, Peter J.}, citeulike-article-id = {6071936}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/12441145}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=12441145}, day = {7}, issn = {1043-4666}, journal = {Cytokine}, keywords = {il-18, neopterin}, month = {October}, number = {1}, pages = {38--48}, posted-at = {2009-11-05 01:35:10}, priority = {2}, title = {Immunopharmacology of recombinant human interleukin-18 in non-human primates.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12441145}, volume = {20}, year = {2002} }

TY - JOUR ID - citeulike:6071936 L3 - citeulike-article-id:6071936 N2 - 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. IS - 1 JF - Cytokine SN - 1043-4666 EP - 48 TI - Immunopharmacology of recombinant human interleukin-18 in non-human primates. VL - 20 SP - 38 KW - il-18 KW - neopterin AU - Herzyk, Danuta AU - Soos, Jeanne AU - Maier, Curtis AU - Gore, Elizabeth AU - Narayanan, Padma AU - Nadwodny, Kimberly AU - Liu, Susan AU - Jonak, Zdenka AU - Bugelski, Peter PY - 2002/10/07/ UR - http://view.ncbi.nlm.nih.gov/pubmed/12441145 ER -