Faculty Collaboration Database

Comparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP). Blood 2003 Jul 15;102(2):436-41

Date

03/22/2003

Pubmed ID

12649145

DOI

10.1182/blood-2003-01-0290

Scopus ID

2-s2.0-0037818706 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

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 microg/kg/d subcutaneously x 7 days) or DDAVP (5 microg/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.

Author List

Olsen EH, McCain AS, Merricks EP, Fischer TH, Dillon IM, Raymer RA, Bellinger DA, Fahs SA, Montgomery RR, Keith JC Jr, Schaub RG, Nichols TC

MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Deamino Arginine Vasopressin
Dogs
Drug Evaluation, Preclinical
Factor VIII
Half-Life
Heart
Heterozygote
Interleukin-11
Myocardium
RNA, Messenger
Recombinant Proteins
Spleen
Weibel-Palade Bodies
von Willebrand Diseases
von Willebrand Factor