title: Immoderate inhibition of estrogen by anastrozole enhances the severity of experimental polyarthritis.
abstract: Aromatase inhibitors have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. Meanwhile, more and more breast cancer patients who are treated with aromatase inhibitors as adjuvant therapies often experience arthralgias and musculoskeletal aching, in some cases, have necessitated discontinuation of treatment. We therefore use a rat model of human RA to test the hypothesis that anastrozole, an aromatase inhibitor, could enhance arthritis. The parameters used for analyzing the disease severity included paw volume, radiology, histopathological examination, markers for cytokine profile, immunophenotypic assays, and immune response to type II collagen. Administration of anastrozole significantly increased the severity of arthritis. Anastrozole induced the increased levels of proinflammatory cytokines, IFN-gamma, IL-12, and the decreased levels of IL-4, IL-10 secretion. We further found that anastrozole suppressed the differentiation of naive T cells to Treg cells, and it blocked the balance of IgG2a/IgG1 in peripheral blood. Meanwhile, estradiol concentration was the lowest in the anastrozole group. In a well-established model of postmenopausal RA, anastrozole potently promote the progression of arthritis and the associated development of osteoporosis. This potential problem should alert the oncologists and other health professionals.
authors.affiliation: Department of Medical Oncology, The Affiliated Tumor Hospital, Harbin Medical University, Harbin 150040, China.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Wang
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shi
authors.initials: S
authors.lastname: Jin
authors.forename: Meiyan
authors.initials: M
authors.lastname: Feng
authors.forename: Xinmei
authors.initials: X
authors.lastname: Kang
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.forename: Shuling
authors.initials: S
authors.lastname: Liu
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000077384:Anastrozole; D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D003094:Collagen; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D009570:Nitriles / Q000494:pharmacology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D012720:Severity of Illness Index; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077384:Anastrozole; D003094:Collagen