PT  - JOURNAL ARTICLE
AU  - Sandra K. Klimuk
AU  - Sean C. Semple
AU  - Patrick N. Nahirney
AU  - Michelle C. Mullen
AU  - C. Frank Bennett
AU  - Peter Scherrer
AU  - Michael J. Hope
TI  - Enhanced Anti-Inflammatory Activity of a Liposomal Intercellular Adhesion Molecule-1 Antisense Oligodeoxynucleotide in an Acute Model of Contact Hypersensitivity
DP  - 2000 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 480--488
VI  - 292
IP  - 2
4099  - http://jpet.aspetjournals.org/content/292/2/480.short
4100  - http://jpet.aspetjournals.org/content/292/2/480.full
SO  - J Pharmacol Exp Ther2000 Feb 01; 292
AB  - The anti-inflammatory activity of free and liposome-encapsulated oligonucleotide targeted against intercellular adhesion molecule-1 mRNA was investigated in a delayed type hypersensitivity model of acute inflammation in mice. Contact hypersensitivity reactions to 2,4-dinitrofluorobenzene were monitored by measuring ear thickness and cellular infiltration, both of which were observed to be maximal 24 h after ear challenge. A murine-specific phosphorothioate oligodeoxynucleotide and various control sequences were each passively encapsulated into 100-nm diameter large unilamellar vesicles composed of egg phosphatidylcholine and cholesterol. All formulations were administered as a single-bolus injection into the tail vein ∼15 min after initiating ear inflammation. Oligodeoxynucleotide dose was varied from 5 to 50 mg/kg and the extent of inflammation was assessed 24 h later. Mice treated with free oligonucleotide, empty vesicles, or encapsulated control sequences showed no measurable effect on ear swelling or cellular infiltration compared with untreated controls. However, mice that received the active sequence encapsulated in lipid vesicles exhibited near baseline levels of ear thickness and leukocyte infiltration, similar to that observed in mice treated with a topical corticosteroid. These data demonstrate the utility of liposome-encapsulated intercellular adhesion molecule-1 antisense oligonucleotide as a novel anti-inflammatory therapeutic. The American Society for Pharmacology and Experimental Therapeutics