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The Toxicology of Interleukin-12: A Review

Safety Assessment, DuPont Pharmaceuticals Company, Newark, Delaware 19714-0030, DuPont Pharmaceuticals, Stine-Haskell Research Center, Building 320, Newark, Delaware 19714-0030, bruce.d.car.2{at}dupontpharma.com.

Vicki M. Eng

Unit of Laboratory Animal Resources, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Jack M. Lipman

Department of Toxicology and Pathology, Hoffinan-La Roche, Nutley, New Jersey 07110

Timothy D. Anderson

Department of Toxicology and Pathology, Hoffinan-La Roche, Nutley, New Jersey 07110

Recombinant murine interleukin (IL)-12 (rmIL-12) exhibits antitumor, antiviral, and antimicrobial activities and can modify allergic inflammatory reactions in animal models. Recombinant human IL-12 (rhIL-12) is currently in clinical trials for treatment of cancer, asthma, and viral hepatitis. Principally a phagocyte-derived cytokine, IL-12 targets natural killer cells and T lymphocytes, stimulating their activity and the secretion of interferon (IFN)-. An understanding of the toxicology of IL-12, due in part to effects mediated by IFN-, has emerged from preclinical safety and mechanistic studies and initial clinical trials. Target organs common to several animal species and humans include the lymphohematopoietic system, intestines, liver, and lung.

Key Words: Interferon- • mouse • guinea pig • squirrel monkey • cynomolgus macaque • chimpanzee • human • hematopoeisis • liver • intestine • lung • IL- 12

Toxicologic Pathology, Vol. 27, No. 1, 58-63 (1999)
DOI: 10.1177/019262339902700112


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