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.
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.
Seggev
J S
JS
Division of Pulmonary, Critical Care, University of Missouri, Columbia.
Sunderrajan
E V
EV
Palomo
T
T
McKenzie
W N
WN
Braun
S R
SR
O'Sullivan
F X
FX
Walker
S E
SE
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*
D007074:Immunoglobulin G; D013739:Testosterone; D004958:Estradiol; D003520:Cyclophosphamide