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Tytuł pozycji:

Do RANKL inhibitors (denosumab) affect inflammation and immunity?

Tytuł :
Do RANKL inhibitors (denosumab) affect inflammation and immunity?
Autorzy :
Ferrari-Lacraz, Sylvie
Ferrari, Serge Livio
Pokaż więcej
Temat :
Osteoprotegerin/pharmacology
Antibodies, Monoclonal/adverse effects/pharmacology
Bone Resorption/physiopathology
Mice
Arthritis, Rheumatoid/physiopathology
musculoskeletal diseases
Tumor Necrosis Factor-alpha/antagonists & inhibitors
Osteoblasts/metabolism
T-Lymphocytes/metabolism
Receptor Activator of Nuclear Factor-kappa B/antagonists & inhibitors
RANK Ligand/adverse effects/pharmacology
Infection/chemically induced
Osteoclasts/metabolism
Neoplasms/chemically induced
Osteoporosis/physiopathology
Animals
Rats
B-Lymphocytes/metabolism
Female
ddc:618.97
Humans
Źródło :
Osteoporosis International, Vol. 22, No 2 (2011) pp. 435-46
Rok publikacji :
2018
Kolekcja :
Archive_ouverte_UNIGE
Archive_ouverte_UNIGE_enriched
RERO_DOC_Digital_Library
RERO_DOC_Digital_Library_enriched
Oryginalny identyfikator :
pmid: 20571772
Język :
English
ISSN :
0937-941X
DOI :
10.1007/s00198-010-1326-y
Receptor activator of nuclear factor kappa B ligand (RANKL) and its natural antagonist, osteoprotegerin (OPG), are, respectively, an indispensable factor and a potent inhibitor for osteoclast differentiation, activity, and survival. The development of a human monoclonal antibody to RANKL, denosumab, constitutes a novel approach to prevent fragility fractures in osteoporosis, skeletal complications of malignancy, and potentially bone erosions in rheumatoid arthritis (RA). In addition to being expressed by osteoblasts, RANKL is abundantly produced by activated T cells, and synoviocytes in RA, whereas its receptor, RANK, is also expressed by monocytes/macrophages and dendritic cells. However, in preclinical and clinical studies of RA-including patients with some degree of immunosuppression-RANKL inhibitors did not significantly alter inflammatory processes. RANKL, RANK, and OPG deficiency in murine models highlights the important role of this pathway in the development and maturation of the immune system in rodents, including functions of T and/or B cells, whereas OPG overexpression in mice and rats seems innocuous with regard to immunity. In contrast, loss-of-function mutations in humans have more limited effects on immune cells. In clinical studies, the overall rate of infections, cancer, and death was similar with denosumab and placebo. Nevertheless, the risk of severe infections and cancer in some specific tissues remains to be carefully scrutinized.

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