Activation of mononuclear cells by interleukin-12: an in vivo study in chimpanzees.
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.
Lauw
F N
FN
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
te Velde
A A
AA
Dekkers
P E
PE
Speelman
P
P
Aerts
J M
JM
Hack
C E
CE
van Deventer
S J
SJ
van der Poll
T
T
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
D015415:Biomarkers; D018664:Interleukin-12; D006596:Hexosaminidases; C086400:chitotriosidase; D053804:Granzymes; D012697:Serine Endopeptidases