Garlic increases IL-10 and inhibits TNFα and IL-6 production in endotoxin-stimulated human placental explants

Abstract

Preeclampsia is a multisystem disorder manifest by hypertension after 20 weeks' gestation associated with end organ damage, usually proteinuria. The placenta is thought to be pivotal in the pathogenesis of the disease. Both the placenta and the maternal systemic response are characterised by heightened inflammation. Garlic has been shown to have anti-inflammatory and pro-apoptotic properties amongst others. It was hypothesised that treating placental explants with garlic may inhibit the production of inflammatory cytokines (interleukin-6 (IL-6) and tumour necrosis factor (TNFalpha)) and stimulate the production of anti-inflammatory cytokines (interleukin-10 (IL-10)) by the placental explants. Garlic, we hypothesised, would also stimulate apoptosis in the explants as measured by soluble TNF-related apoptosis-inducing ligand/Apo-2L (sTRAIL) production. Normal placental explants (n=5) and explants from women who had preeclampsia (n=4) were cultured in the presence of various garlic concentrations (10-1000 microg/mL). The lowest garlic concentration (10 microg/mL) increased the normal explant production of IL-10 by 29.2% (12.2, 57.5%; p<0.01) while inhibiting the production of IL-6 by 23.5% (8.9, 32.5%; p<0.01) (normal explants) and TNFalpha by 19.4% (4.5, 35.3%; p<0.05) (preeclamptic explants). Garlic resulted in an increase in IL-10 production at lower doses (normal explants only) and inhibition of the production of IL-10 at higher doses (normal and preeclamptic explants). Garlic also resulted in a dose-dependent reduction of IL-6 and TNFalpha. Initially there was no change in sTRAIL production; however, at the highest garlic concentrations there was a significant increase in production. We thus conclude that garlic may have an immunomodulatory effect on normal and preeclamptic placentas.