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Henry SP, Levin AA, White K, et al. Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice. J Immunotoxicol. 2006;3(4):199-211doi: 10.1080/15476910601046538.
Henry, S. P., Levin, A. A., White, K., & Mennear, J. H. (2006). Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice. Journal of immunotoxicology, 3(4), 199-211. https://doi.org/10.1080/15476910601046538
Henry, Scott P, et al. "Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice." Journal of immunotoxicology vol. 3,4 (2006): 199-211. doi: https://doi.org/10.1080/15476910601046538
Henry SP, Levin AA, White K, Mennear JH. Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice. J Immunotoxicol. 2006 Dec 01;3(4):199-211. doi: 10.1080/15476910601046538. PMID: 18958701.
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J Immunotoxicol. 2006 Dec 01;3(4):199-211. doi: 10.1080/15476910601046538.

Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice.

Journal of immunotoxicology

Scott P Henry, Arthur A Levin, Kimber White, John H Mennear

Affiliations

  1. ISIS Pharmaceuticals, Inc., Carlsbad, California 92008, USA. [email protected]

PMID: 18958701 DOI: 10.1080/15476910601046538

Abstract

ISIS 2302 is a phosphorothioate oligonucleotide designed to inhibit human ICAM-1 and is intended for treatment of inflammatory diseases. Molecules of this class are known to elicit pro-inflammatory effects, and immunotoxicity studies were performed in mice to elucidate the nature of effects of ISIS 2302 on mammalian immune function. ISIS 2302 (1, 5, 20, or 50 mg/kg/dose) was administered intravenously every other day for 27 days. The pro-inflammatory properties of the drug were observed at doses > or = 20 mg/kg. A dose-dependent increase in spleen weight was associated with increased absolute splenocyte and B-lymphocyte counts after the 50 mg/kg/dose regimen. The mitogenic response of B-lymphocytes to bacterial lipopolysaccharide was increased after the 20 and 50 mg/kg/doses but antibody-forming cell activities remained unchanged. Total serum IgG concentration was decreased after the 20 and 50 mg/kg/dose regimens but IgM titers were unchanged. Increases in IL-6, IL-12, and MCP-1 as well as NK cell activity were observed after administration of 20 and 50 mg/kg/dose. Cytotoxic T-lymphocyte activity was decreased by the 50 mg/kg/dose regimen. Other changes in immune function were not observed in ISIS 2302-dosed mice. ISIS 3082, a murine active ICAM-1 inhibitor, was used to demonstrate the anti-inflammatory activity of ICAM-1 inhibition in the 2,4-dinitrofluorobenzene-induced contact sensitization model. Intravenous administration of 1 mg/kg of ISIS 3082 every other day for 27 days was unequivocally anti-inflammatory in the contact sensitization test. The results of these experiments support the conclusion that the prophlogistic effects of ISIS 2302 in mice are observed only at suprapharmacologic doses.

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