Age-Dependent Effects of Prenatal Dexamethasone Exposure on Immune Responses in Male Rats.
Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes. The production of innate and adaptive immune cytokines was assessed from the culture supernatants of splenocytes, stimulated with lipopolysaccharide and concanavalin A, respectively. For innate cytokines, the levels of interferon gamma inducible protein 10 were significantly higher, but those of tumor necrosis factor-α were significantly lower, in the culture medium of splenocytes prepared from the DEX group at D120 than those in the VEH group. For adaptive cytokines, the levels of interleukin-4 (IL-4) were significantly higher at D7 and those of IL-10 were significantly higher at D120 after prenatal exposure to DEX. We also showed that the expression level of IL-4 mRNA was significantly higher in splenocytes prepared from the DEX group at D7, compared with the VEH group. Importantly, the mRNA expression level of T-bet, a key transcription factor for immune cells, was greatly decreased in the spleen of the DEX group at D7, compared with the VEH group. In conclusion, prenatal dexamethasone exposure shows the greater impact on immune responses of their male offspring in early life.
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center.
Ming-Yi
MY
Chou
Li-Tung
LT
Huang
You-Lin
YL
Tain
Ho-Chang
HC
Kuo
Mao-Meng
MM
Tiao
Jiunn-Ming
JM
Sheen
Chih-Cheng
CC
Chen
Pi-Lien
PL
Hung
Kai-Sheng
KS
Hsieh
Hong-Ren
HR
Yu
D000375:Aging / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D006657:Histones / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D007070:Immunoglobulin A / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008221:Lymphoid Tissue / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000276:immunology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D000098815:T-bet Transcription Factor
D006657:Histones; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone