Prenatal administration of indomethacin modulates Th2 cytokines in juvenile rats.
Indomethacin (IND) suppresses the T-dependent antibody response (TDAR) in juvenile males when it is administered to pregnant rats during late gestation. In this study, the effect of IND on cytokine production in juvenile rats was examined to investigate the mechanism behind the suppression of antibody production. IND was orally administered to pregnant SD rats on days 18-21 of gestation. After parturition, the spleen cells isolated from 3-week-old pups were incubated with concanavalin A (Con A) or lipopolysaccharide (LPS). The level of cytokines in the culture supernatant was measured. IL-10 decreased significantly in the males, and IL-6 and TNF-alpha tended to decrease in both sexes. In order to examine the effect of IND on cytokine production in juvenile rats in vitro, spleen cells isolated from untreated 3-week-old rats were exposed to IND and a mitogen (Con A or LPS) simultaneously, and then the levels of cytokines were measured. IL-4 decreased in the males, and IL-6 tended to decrease in both sexes. These results indicated that treating dams with IND during late gestation causes a change in the release of Th2 cytokine, and suggested that this change involves the suppression of antibody production.
Kushima
Kiyoshi
K
Drug Safety Research Laboratories, Astellas Pharma Inc., 1-6, Kashima 2-chome, Yodogawa-ku, Osaka, Japan.
Sakuma
Shozo
S
Furusawa
Shuichi
S
Fujiwara
Michio
M
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007213:Indomethacin / Q000633:toxicity*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D007213:Indomethacin