Ueland T, Frøland S S, Bollerslev J, Aukrust P
Research Institute for Internal Medicine, National University Hospital, Oslo, Norway.
Eur J Clin Invest. 2001 Jan;31(1):72-8. doi: 10.1046/j.1365-2362.2001.00768.x.
Based on the involvement of cytokines and growth factors in bone homeostasis, we hypothesised that patients with common variable immunodeficiency (CVI), characterised by persistent immune activation in vivo, may have disturbed bone metabolism as evaluated by biochemical markers of bone turnover.
Serum levels of tumour necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), bone-specific alkaline phosphatase (B-ALP), osteocalcin, carboxyterminal crosslinking telopeptide of type I collagen (CTX-I), insulin-like growth factor (IGF)-I and IGF binding protein-3 (IGFBP-3) were measured in 25 patients with CVI and compared to 25 age- and sex-matched healthy controls.
Patients with CVI had significantly higher serum levels of CTX-I and B-ALP, and significantly lower serum levels of IGF-I and IGFBP-3 compared to controls as shown in cross-sectional, and as for B-ALP and CTX-I, also during longitudinal testing. No differences were observed for osteocalcin between the two groups. The elevated B-ALP and decreased IGF-I and IGFBP-3 levels were most pronounced in a subgroup of CVI patients characterised by persistent activation of proinflammatory cytokines in vivo. Raised B-ALP and decreased IGF-I and IGFBP-3 were also significantly correlated with enhanced IL-6 and TNF-alpha levels in these patients.
The present study suggests that persistent immune activation in vivo, with raised levels of proinflammatory cytokines, may be related to disturbed bone homeostasis in CVI patients, further supporting an interaction between immune related mediators and bone metabolism in humans.
基于细胞因子和生长因子参与骨稳态调节，我们推测，以体内持续免疫激活为特征的普通可变免疫缺陷（CVI）患者，通过骨转换生化标志物评估可能存在骨代谢紊乱。
测定25例CVI患者血清肿瘤坏死因子α（TNFα）、白细胞介素-6（IL-6）、骨特异性碱性磷酸酶（B-ALP）、骨钙素、I型胶原羧基末端交联肽（CTX-I）、胰岛素样生长因子（IGF）-I和IGF结合蛋白-3（IGFBP-3）水平，并与25例年龄和性别匹配的健康对照者进行比较。
与对照组相比，CVI患者血清CTX-I和B-ALP水平显著升高，IGF-I和IGFBP-3水平显著降低，横断面研究如此，纵向检测时B-ALP和CTX-I亦是如此。两组间骨钙素水平无差异。在体内促炎细胞因子持续激活的CVI患者亚组中，B-ALP升高以及IGF-I和IGFBP-3降低最为明显。这些患者中，B-ALP升高以及IGF-I和IGFBP-3降低也与IL-6和TNF-α水平升高显著相关。
本研究提示，体内持续免疫激活以及促炎细胞因子水平升高可能与CVI患者骨稳态紊乱有关，进一步支持了免疫相关介质与人类骨代谢之间的相互作用。
