Expression of human IL-1alpha after intramarrow gene transfer into healthy non-human primate by adenoviral vector.
Interleukin-1alpha (IL-1alpha) is a multifunctional cytokine that stimulates myelopoiesis in macaque. However, daily systemic injections of IL-1alpha are associated with severe side effects. We therefore investigated the feasibility of a gene therapy strategy aimed at increasing the IL-1alpha local production in bone marrow with limited release of the vector into the blood circulation. Intra-medullar administration of adenoviral vector containing human IL-1alpha (huIL-1alpha) gene resulted in enhanced neutrophil, monocyte and platelet counts during the two first weeks after injection. The DNA vector, the transgene expression and the huIL-1alpha production was detected in treated bone marrow without significant detection of huIL-1alpha in the peripheral blood. Associated with huIL-1alpha production, we observed concomitant plasma C reactive protein and IL-1Ra peaks in the acellular fraction of treated bone marrow at days 3 and 7. No abnormal clinical side effects were observed in any of the animals following the adenoviral vector injection.
Bécard
Nicolas
N
Commissariat à l'Energie Atomique, Laboratoire d'Immuno-Pathologie Experimentale, Service de Neurovirologie, CRSSA, EPHE, IPSC, 18 route du panorama, 92265 Fontenay-aux-Roses Cedex, France.
de Revel
Thierry
T
Sorg
Tania
T
Dormont
Dominique
D
Le Grand
Roger
R
D000256:Adenoviridae; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D008252:Macaca fascicularis / Q000378:metabolism*; D008297:Male; D008436:Mauritius; D021141:Nucleic Acid Amplification Techniques; D019076:Transgenes / Q000235:genetics
D017931:DNA Primers; D007375:Interleukin-1; D002097:C-Reactive Protein