Da Silva J A, Larbre J P, Seed M P, Cutolo M, Villaggio B, Scott D L, Willoughby D A
Department of Experimental Pathology, St. Bartholomew's Hospital Medical College, London.
J Rheumatol. 1994 Feb;21(2):330-7.
To investigate sex differences in granulomatous inflammation and its effects upon articular cartilage and to assess the potential role of sex steroids in the process.
The cotton-pellet cartilage implant model was used with male and female mice in the presence and absence of gonadectomy and hormone replacement. The effects of granulomatous tissue upon articular cartilage was assessed and tissue content of interleukin 1 (IL-1) was determined. The expression of sex hormone receptors in inflammatory tissue was investigated by immunocytochemistry.
Female mice showed a higher ability than males to degrade cartilage irrespective of the sex of the cartilage implanted. Gonadectomy resulted in a significant acceleration of cartilage damage in both sexes, which was reverted by estrogen replacement in females and androgen replacement in males. Female granulomata had significantly higher IL-1 content than those from males. Gonadectomy was associated with an increased IL-1 content in males but not in females, the effects being abolished by androgen replacement in males. Estrogen and androgen receptors were identified in inflammatory cells from the granulomatous tissue.
Our data demonstrate that sex hormones affect inflammation induced cartilage degradation in male and female mice probably through the modulation of cytokine production and release in the granulomatous tissue. Further investigation on the effects of sex steroids in inflammation induced cartilage degradation may help elucidate their pathogenic role and therapeutic potential in human disease.
研究肉芽肿性炎症中的性别差异及其对关节软骨的影响,并评估性类固醇在该过程中的潜在作用。
采用棉粒软骨植入模型,对雄性和雌性小鼠进行去势和激素替代处理,观察有无这些处理的情况。评估肉芽肿组织对关节软骨的影响,并测定白细胞介素1(IL-1)的组织含量。通过免疫细胞化学研究炎症组织中性激素受体的表达。
无论植入的软骨性别如何,雌性小鼠降解软骨的能力均高于雄性。去势导致两性软骨损伤显著加速,雌性用雌激素替代、雄性用雄激素替代可逆转这种情况。雌性肉芽肿的IL-1含量显著高于雄性。去势使雄性IL-1含量增加,但对雌性无影响,雄性用雄激素替代可消除这种影响。在肉芽肿组织的炎症细胞中鉴定出雌激素和雄激素受体。
我们的数据表明,性激素可能通过调节肉芽肿组织中细胞因子的产生和释放,影响雄性和雌性小鼠炎症诱导的软骨降解。进一步研究性类固醇在炎症诱导的软骨降解中的作用,可能有助于阐明它们在人类疾病中的致病作用和治疗潜力。