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Anti-inflammatory cytokine profile in term placentae of HIV-1 infected women receiving antiretrovirals for the prevention of mother-to-child transmission in Thailand
Presented by Sakorn Pornprasert, Thailand.
Pornprasert S.1, Mary J.-Y.2, Faye A.3, Leechanachai P.1, Limtrakul A.4, Rugpao S.5, Sirivatanapa P.5, Gomuthbutra V.6, Matanasaravoot W.7, Le Coeur S.8, Lallemant M.9, Barré-Sinoussi F.10, Menu E.10, Ngo-Giang-Huong N.9
1Faculty of Associated Medical Sciences, Chiang Mai University, Chiang-Mai, Thailand, 2INSERM U717, Université Paris 7, Paris, France, 3INSERM U131, Paris, France, 4Health Promotion Center Region 10 Hospital, Chiang-Mai, Thailand, 5Faculty of Medicine, Chiang Mai University, Chiang-Mai, Thailand, 6Nakornping Hospital, Chiang-Mai, Thailand, 7Lamphun Hospital, Chiang-Mai, Thailand, 8Institut National d’Etudes Démographiques, Paris, France, 9Institut de Recherche pour le Développement, UMI 174/ PHPT, Paris, France, 10Institut Pasteur, Paris, France
Objectives: To analyze placental cytokine balance in HIV-1 infected women who received antiretrovirals for prevention of HIV-1 mother-to-child transmission.
Methods: Placentae were collected from 88 HIV-1 infected women. Cytokine secretion and mRNA expression profile were quantified in 24h-culture supernatants and placental explants using ELISA and real-time PCR, respectively. The median levels or proportions of secretion values above the detection limit were compared according to the mode of delivery (elective caesarean section vs. vaginal), antiretroviral prophylaxis regimen (zidovudine only vs. zidovudine plus a single dose of nevirapine at delivery), duration of zidovudine prophylaxis during pregnancy (9 weeks or less vs. more) and time to delivery after nevirapine intake (5 hours or more vs. less).
Results: Median of TNF-alpha mRNA expression was about two times lower in women who received zidovudine plus nevirapine compared to women who received zidovudine only (p=0.01) and in women with vaginal delivery compared to caesarean section (p=0.005). Moreover, long zidovudine prophylaxis duration was associated with a lower median of TNF-alpha mRNA expression (p=0.003) and a higher proportion of detectable IL-10 secretion levels (p<0.001). This proportion was also higher when nevirapine was given less than 5h prior to delivery (p=0.009). Effect on IL-10 secretion appeared to be independent of the mode of delivery, while effect on TNF-alpha mRNA expression might result from nevirapine, mode of delivery or both.
Conclusions: Zidovudine plus nevirapine modified the TNF-alpha/IL-10 balance in the placental environment in favor of an anti-inflammatory profile. This effect might represent another mechanism of antiretrovirals, in controlling HIV-1 replication at the level of the placental barrier and thus preventing maternal-foetal transmission.
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