Immune system and bone metabolism: Does thymectomy influence postmenopausal bone loss in humans?
Recent studies of animal models have suggested that an increase in the number of T cells due to both peripheral expansion and increased thymic T cell output plays a key role in the regulation of bone loss after ovariectomy. Osteoclastogenic cytokines which are either produced by T cells or activate T cells have also been implicated in ovx induced bone loss. Among them are TNF alpha and IL-7. The present study investigates the role of thymectomy (THX) and IL-7 in bone metabolism in humans. We studied T cells subsets, cytokine production and bone metabolism in 13 women thymectomized for Myasthenia gravis as compared to healthy controls. Our data demonstrate that the number of CD4+ and TNF-producing T cells is lower in THX women as compared to euthymic controls. However in THX women the residual T cells produce higher levels of IL-7 and RANKL. Furthermore, flow cytometry shows that IL-7 is produced by T and B cells. Serum levels of TNF alpha were unaffected by THX and both serum TNF alpha and the RANKL/OPG correlated inversely with BMD. There were no differences in bone turnover and bone mineral density between THX women and the controls. These data suggest that THX decreases the number of TNF-producing CD4+ T cells but does not alters serum TNF levels. The RANKL/OPG ratio and indices of bone metabolisms are also not affected by THX, although THX increases the levels of IL-7 and RANKL. Further studies are needed to clarify the role of thymus in bone metabolism and osteoclastogenesis in postmenopausal women.
D'Amelio
Patrizia
P
Department of Internal Medicine, Research-University of Torino, Italy. patrizia.damelio@unito.it
Grimaldi
Anastasia
A
Bernabei
Paola
P
Pescarmona
Gian Piero
GP
Isaia
Giancarlo
G
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D015519:Bone Density; D002352:Carrier Proteins / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007107:Immune System / Q000276:immunology*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000276:immunology* / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013934:Thymectomy
D015415:Biomarkers; D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human