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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2003-01-0290. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0290v1 102/2/436    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Olsen, E. H. N. Articles by Nichols, T. C. Search for Related Content PubMed PubMed Citation Articles by Olsen, E. H. N. Articles by Nichols, T. C. Related Collections Plenary Papers Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 436-441 PLENARY PAPERS Comparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP) Eva H. N. Olsen, Arlene S. McCain, Elizabeth P. Merricks, Thomas H. Fischer, Ivy M. Dillon, Robin A. Raymer, Dwight A. Bellinger, Scot A. Fahs, Robert R. Montgomery, James C. Keith, Jr, Robert G. Schaub, and Timothy C. Nichols From the Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill; Medical College of Wisconsin, Milwaukee; and Wyeth Research, Cambridge, MA. Recombinant human interleukin-11 (rhIL-11), a glycoprotein 130 (gp130)–signaling cytokine approved for treatment of thrombocytopenia, also raises von Willebrand factor (VWF) and factor VIII (FVIII) by an unknown mechanism. Desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP]) releases stored VWF and FVIII and is used for treatment of VWF and FVIII deficiencies. To compare the effect of these 2 agents, heterozygous von Willebrand disease (VWD) and normal dogs were treated with either rhIL-11 (50 µg/kg/d subcutaneously x 7 days) or DDAVP (5 µg/kg/d intravenously x 7 days). The rhIL-11 produced a gradual and sustained elevation of VWF and FVIII levels in both heterozygous VWD and normal dogs while DDAVP produced a rapid and unsustained increase. Importantly, rhIL-11 treatment produced a 2.5- to 11-fold increase in VWF mRNA in normal canine heart, aorta, and spleen but not in homozygous VWD dogs, thus identifying a mechanism for elevation of plasma VWF in vivo. Moreover, dogs pretreated with rhIL-11 retain a DDAVP-releasable pool of VWF and FVIII, suggesting that rhIL-11 does not significantly alter trafficking of these proteins to or from storage pools. The half-life of infused VWF is unchanged by rhIL-11 in homozygous VWD dogs. These results show that rhIL-11 and DDAVP raise plasma VWF by different mechanisms. Treatment with rhIL-11 with or without DDAVP may provide an alternative to plasma-derived products for some VWD and hemophilia A patients if it is shown safe in clinical trials. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: DDAVP and interleukin-11: a boosting combination Peter J. Lenting and Jan J. Sixma Blood 2003 102: 415-416. [Full Text] [PDF] This article has been cited by other articles: S. F. De Meyer, H. Deckmyn, and K. Vanhoorelbeke von Willebrand factor to the rescue Blood, May 21, 2009; 113(21): 5049 - 5057. [Abstract] [Full Text] [PDF] A. H. James, M. 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[Abstract] [Full Text] [PDF] S. L. Haberichter, E. P. Merricks, S. A. Fahs, P. A. Christopherson, T. C. Nichols, and R. R. Montgomery Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells Blood, January 1, 2005; 105(1): 145 - 152. [Abstract] [Full Text] [PDF] T. S. Lin, I. W. Flinn, R. Modali, T. A. Lehman, J. Webb, S. Waymer, M. E. Moran, M. S. Lucas, S. S. Farag, and J. C. Byrd FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia Blood, January 1, 2005; 105(1): 289 - 291. [Abstract] [Full Text] [PDF] P. M. Mannucci Treatment of von Willebrand's Disease N. Engl. J. Med., August 12, 2004; 351(7): 683 - 694. [Full Text] [PDF]

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