Estriol has different effects from 17β-estradiol in modulating mouse splenocyte function under inflammatory conditions

Abstract

Estriol (E3), an endogenous estrogen predominantly produced during human pregnancy, has been suggested to play an important role in modulating the immune system function during pregnancy. The present study sought to investigate the ability of E3 to alter splenocyte functions in non-immunized naïve BALB/c female mice and also in mice injected with complete Freund’s adjuvant (CFA), and the effect of E3 was compared with that of 17β-estradiol (E2). When mice were injected with CFA, their spleen weight index (i.e., wet organ wet/whole body weight) was increased by ~ 300%, but co-administration of E3 almost completely suppressed splenomegaly. E3 also reduced cytokine production and reduced ERK and p38 activation in both splenocytes and peritoneal exudate cells from CFA-treated animals. In comparison, while E2 had a similar but slightly weaker effect than E3 in reducing splenomegaly, it had a rather different effect from E3 on cytokine production and ERK activation in splenocytes and peritoneal exudate cells from CFA-treated mice. Under naïve immunological conditions, E3 and E2 had very similar effects on splenocyte functions. Both of them transiently increased the percentages of splenic CD4+ and CD8+ cells. They also increased the proliferation of splenocytes ex vivo, and stimulated production of interferon-γ and interleukin-2. Altogether, these data show that E3 and E2 have different effects on splenocyte functions when the animals are under experimentally induced inflammatory conditions.