Pulmonary delivery of interleukin-7 provides efficient and safe delivery to the aging immune system.

Details

Serval ID
serval:BIB_AE1F0662221A
Type
Article: article from journal or magazin.
Collection
Publications
Title
Pulmonary delivery of interleukin-7 provides efficient and safe delivery to the aging immune system.
Journal
Rejuvenation Research
Author(s)
Mitchell W.A., Castells A., Lang P.O., Matas E., Lapenna A., Aspinall R.
ISSN
1557-8577 (Electronic)
ISSN-L
1549-1684
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
15
Number
4
Pages
414-422
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
Age-associated atrophy of the thymus with coincident reduction in thymopoeisis, decline in thymic output, and subsequent immune dysfunction has been reversed by the use of interleukin-7 (IL-7). In the earlier studies and in clinical trials, delivery of IL-7 has been by multiple injections over several days to maintain effective activity levels in the tissues. This is unlikely to meet with high compliance rates in future clinical use, and so we tested alternate routes of delivery using a technique involving tagging IL-7 with fluorescent dye that emits in the near-infrared region and whose fluorescence can be visualized within the tissues of live animals. We have shown that intratracheal instillation, enabling transfer through the lungs, provides an effective route for delivering IL-7 into the bloodstream and from there into the tissues in older animals. Delivery is rapid and widespread tissue distribution is seen. Comparison of administration either subcutaneously or by instillation reveals that IL-7 delivery by the pulmonary route provides significantly greater transmission to lymphoid tissues when compared with injection. In functional assessment studies, pulmonary administration led to significantly improved intrathymic T cell development in older animals when compared with IL-7 delivered by injection. Furthermore, in these older animals, delivery of IL-7 by intratracheal instillation was not accompanied by any apparent adverse events when compared with controls receiving saline vehicle by instillation or animals receiving IL-7 by subcutaneous injection.
Keywords
Administration, Inhalation, Aging/immunology, Aging/metabolism, Animals, Female, Immune System, Instillation, Drug, Interleukin-7/administration & dosage, Interleukin-7/metabolism, Mice, Mice, Inbred C57BL, Tissue Distribution, Trachea
Pubmed
Web of science
Create date
15/04/2015 8:17
Last modification date
20/08/2019 15:17
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