Distinct biological activities of recombinant forms of human interleukin-2 in vivo View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-02-01

AUTHORS

A. B. Lentsch, Koji Nakagawa, Hiroyuki Yoshidome, Alexandra Gerassimides, Frederick N. Miller, Michael J. Edwards

ABSTRACT

The biological activity of all recombinant forms of interleukin-2 (IL-2) is based upon an in vitro lymphocyte proliferation assay and measured in international units (IU). Numerous in vitro investigations have suggested that there may be different cellular effects of recombinant human IL-2 retaining the natural sequence (nIL-2) as compared to another recombinant form containing a serine substitution at amino acid position 125 ([Ser]IL-2). In the present study we investigated whether nIL-2 and [Ser]IL-2 cause similar patterns of systemic toxicities. C57BL/6 mice were treated with identical doses of either nIL-2 or [Ser]IL-2, as measured in IU, for 3 days and had blood and tissues removed for analysis of lymphocyte activation and organ dysfunction. The administration of nIL-2 had considerably greater effects on lymphocyte activation than did [Ser]IL-2, causing much greater up-regulation of the α subunit of the IL-2 receptor and the adhesion molecule lymphocyte function-associated antigen-1. Furthermore, nIL-2 induced more organ edema than did [Ser]IL-2 and caused hepatocellular injury, which was absent in mice treated with [Ser]IL-2. These data demonstrate that equivalent doses, measured in IU, of nIL-2 and [Ser]IL-2 have profoundly different effects on the induction of organ toxicity, suggesting that the IU standard may not be appropriate for the measurement of many in vivo biological activities. More... »

PAGES

331-336

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s002620050341

DOI

http://dx.doi.org/10.1007/s002620050341

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018838597

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9067404


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204 schema:name Department of Pathology, University of Louisville, Louisville, Kentucky 40292, USA, US
205 Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky 40292, USA, US
206 Department of Surgery, University of Louisville, Louisville, Kentucky 40292, USA, US
207 rdf:type schema:Organization
 




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