Regulatory effects of osteoprotegerin on cellular and humoral immune responses.
The interaction between receptor activator of nuclear factor-kappaB ligand (RANKL) and RANK has been reported to regulate immunity in addition to bone metabolism. The aim of this study was to determine if osteoprotegerin (OPG), an inhibitor of the RANKL-RANK interaction and possibly a new drug against osteoporosis, would adversely affect immunity. OPG was used to treat mice developing different models of cellular and humoral immune responses and also in vitro in T and B cell assays. In mice, OPG does not affect cell-mediated reactions such as contact hypersensitivity to the hapten oxazolone and liver damage, granuloma formation, and infectious load induced by mycobacterial infection. However, OPG increases humoral reactions such as the production of IgM, IgG, and IgE against the T cell dependent antigen keyhole limpet hemocyanin and the production of IgM against the T cell independent antigen Pneumovax. In vitro, OPG modestly co-stimulates T cells but does not affect the proliferation of B cells. OPG has modest immunoregulatory effects that seem to be confined to the humoral response to specific antigens.
Stolina
Marina
M
Amgen Inc, Thousand Oaks, CA 91320, USA. mstolina@amgen.com
Guo
Jane
J
Faggioni
Raffaella
R
Brown
Heather
H
Senaldi
Giorgio
G
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000187:drug effects / Q000276:immunology; D053244:Osteoprotegerin; D010081:Oxazolone / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D006023:Glycoproteins; D007136:Immunoglobulins; D053244:Osteoprotegerin; D022242:Pneumococcal Vaccines; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; D010081:Oxazolone; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin