title: Pulmonary perivascular and interstitial inflammation in MRL/MpJ-lpr/lpr mice. III. Modulation by cyclophosphamide and sex hormones in 4- and 6-month-old animals.
abstract: Estradiol (E) abolished clearing of pulmonary inflammation in 2-month-old male MRL/MpJ-lpr/lpr (MRL/l) mice treated with cyclophosphamide (CY). To determine if this effect persisted in animals with advanced disease, we studied male and female MRL/l mice, aged 4 and 6 months (4M, 6M, 4F, and 6F, respectively). Mice were treated, beginning at 1 month of age, with saline, CY (12 mg/kg/day), CY + castration, CY + castration + testosterone (T) in females, and CY + castration + E in males. CY had no effect on pulmonary inflammation in 4M, possibly because of the development of relatively mild lesions. However, CY was highly effective in 6M. CY + castration + T significantly reduced overall inflammation in 6F and showed a trend in 4F. CY alone had a variable effect on bronchoalveolar lavage fluid (BALF) cells and BALF IgG in both males and females. However, concurrent treatment with T was required for histologic changes of pulmonary inflammation to fully respond to a high dose of CY in female mice. E-treated males had reduced responsiveness to CY.
authors.affiliation: Division of Pulmonary, Critical Care, University of Missouri, Columbia.
authors.forename: J S
authors.initials: JS
authors.lastname: Seggev
authors.forename: E V
authors.initials: EV
authors.lastname: Sunderrajan
authors.forename: T
authors.initials: T
authors.lastname: Palomo
authors.forename: W N
authors.initials: WN
authors.lastname: McKenzie
authors.forename: S R
authors.initials: SR
authors.lastname: Braun
authors.forename: F X
authors.initials: FX
authors.lastname: O'Sullivan
authors.forename: S E
authors.initials: SE
authors.lastname: Walker
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002369:Castration; D003520:Cyclophosphamide / Q000494:pharmacology*; D004195:Disease Models, Animal; D004336:Drug Antagonism; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008297:Male; D051379:Mice; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D007074:Immunoglobulin G; D013739:Testosterone; D004958:Estradiol; D003520:Cyclophosphamide