title: Activation of mononuclear cells by interleukin-12: an in vivo study in chimpanzees.
abstract: Interleukin (IL)-12 is considered a central regulator of host resistance against a variety of pathogens. Therefore, IL-12 has been advocated as a potential therapeutic agent in infections. To determine the in vivo effects of IL-12 on mononuclear cells involved in the host immune response, four chimpanzees received an intravenous injection of recombinant IL-12 (1 microgram/kg). IL-12 induced a sustained decrease in lymphocyte counts, with decreases in CD3+/CD4+ and CD3+/CD8+ cells, while monocyte counts showed a transient increase. IL-12 injection resulted in a shift toward a Th1-mediated immune response as indicated by increased interferon-gamma production during whole-blood stimulation, while not influencing IL-4 production. IL-12-induced activation of NK cells and phagocytes, as indicated by increased NK cell cytotoxicity and increased plasma levels of granzymes A and B and of chitotriosidase activity. These data support the hypothesis that IL-12 may serve as a useful therapeutic agent in infections where a cell-mediated response is protective.
authors.affiliation: Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: F N
authors.initials: FN
authors.lastname: Lauw
authors.forename: A A
authors.initials: AA
authors.lastname: te Velde
authors.forename: P E
authors.initials: PE
authors.lastname: Dekkers
authors.forename: P
authors.initials: P
authors.lastname: Speelman
authors.forename: J M
authors.initials: JM
authors.lastname: Aerts
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: S J
authors.initials: SJ
authors.lastname: van Deventer
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D015415:Biomarkers; D003602:Cytotoxicity, Immunologic; D053804:Granzymes; D006596:Hexosaminidases / Q000097:blood; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D018655:Lymphocyte Count; D009000:Monocytes / Q000166:cytology; D002679:Pan troglodytes / Q000276:immunology*; D010586:Phagocytes; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D015415:Biomarkers; D018664:Interleukin-12; D006596:Hexosaminidases; C086400:chitotriosidase; D053804:Granzymes; D012697:Serine Endopeptidases