Background Etanercept interferes with the tumor necrosis factor (TNF) and is widely used in various autoimmune diseases. However, its developmental toxicity has not been fully established.
Objectives To analyze the effects of etanercept, new generation biological agent used in the therapy of rheumatoid arthritis, on the selected parameters of rat placenta – both in healthy females and in animals with experimentally induced arthritis.
Methods This study included seven groups of Wistar rats: 1) with experimentally induced arthritis (group R), 2-3) with the arthritis treated with etanercept (0.4 or 4.0 mg/kg b.w.; groups RE1 and RE2), 4-5) receiving etanercept despite the lack of arthritis (E1, E2), and 6-7) controls receiving placebo (C1, C2). Female rats were immunized according to the Trentham's method. The drug (0.4 and 4.0 mg/kg) was subcutaneously injected to animals that exhibited one or higher severity score in the visual system for evaluation of CIA rodent model. After the last injection all the females were inseminated and pregnant animals were kept without any xenobiotics until gestational day 21 when cesarean section was performed. Parallel CIA, etanercept-exposed animals without CIA and untreated (sham operated) females were also examined.
Morphological and histological structure of placenta, immunohistochemical reaction of placental homogenates to genes encoding tumor necrosis factor (TNF), cyclooxygenase 1 (COX-1), and proliferating cells nuclear antigen (PCNA), concentration of TNF in placental homogenates, placental expression of interleukin encoding genes: IL1α, IL1β, LTβ, IL6, COX-1, and TNF.
Results Concentrations of TNF were significantly higher in placental homogenates from females with experimentally induced arthritis (groups R, RE1, and RE2). On detailed analysis of these three groups, the concentration of examined cytokine proved significantly higher in animals that did not receive etanercept (group R). The only significant intergroup difference in qualitative expression of examined genes pertained to IL1α gene, the presence of which could be observed solely in placentas of rats from group R.
Conclusions Experimentally induced arthritis causes inflammatory response within the placenta. This effect is partially reversed by etanercept administration; the application of this agent does not negatively affect placental function and morphology.
Disclosure of Interest None declared