Comments for:
Abstract
The placenta may play a critical role in inhibiting vertical transmission of HIV-1. Here we demonstrate that leukemia inhibitory factor (LIF) is a potent endogenous HIV-1–suppressive factor produced locally in placentae. In vitro, LIF exerted a potent, gp130-LIFRβ–dependent, HIV coreceptor–independent inhibition of HIV-1 replication with IC50 values between 0.1 pg/ml and 0.7 pg/ml, depending on the HIV-1 isolate. LIF also inhibited HIV-1 in placenta and thymus tissues grown in ex vivo organ culture. The level of LIF mRNA and the incidence of LIF protein–expressing cells were significantly greater in placentae from HIV-1–infected women who did not transmit HIV-1 to their fetuses compared with women who transmitted the infection, but they were not significantly different from placentae of uninfected mothers. These findings demonstrate a novel pathway for endogenous HIV suppression that may prove to be an effective immune therapy for HIV infection.
Authors
Bruce K. Patterson, Homira Behbahani, William J. Kabat, Yvonne Sullivan, Maurice R.G. O’Gorman, Alan Landay, Zareefa Flener, Nadia Khan, Ram Yogev, Jan Andersson
Would progesterone protect against or stimulate vertical transmission of HIV?
Submitter: Kees Boer | k.boer@amc.uva.nl
Academic Medical Center, Amsterdam
Published June 28, 2001
Dear Sir,
I found the study by Patterson et al (1) on the protecting effect of placental leukemia inhibiting factor (LIF) against transmission of HIV from mother to child most intriguing. They suggested that progesterone by stimulating IL4 would increase the expression of LIF and might thus be a novel weapon against vertical transmission. Progesterone has been studied before for its role in transmission of HIV- like Simian Immunodeficiency Virus (SIV) in the macaque, since postmenopausal women and women who use injectable, progestin-based contraceptives are at increased risk of HIV infection (2). Progesterone implants thinned the vaginal epithelium and enhanced SIV vaginal transmission 7.7-fold (3). Estrogen treatment of ovariectomized macaques protected against SIV infection (2). Also vertical transmission (towards daughters) during the process of birth might occur in part by infection via the vaginal mucosa (4), which sheds some doubts on the potential of progesterone treatment. Moreover, plasma viral RNA was elevated for the first three months in macaques with progesterone implants (3), which does seem to favour this approach without thorough investigations in animal models.
1: Patterson BK, Behbahani H, Kabat WJ, Sullivan Y, O'Gorman MR, Landay A, Flener Z, Khan N, Yogev R, Andersson J Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentae from nontransmitting women. J Clin Invest 2001 Feb; 107: 287-94.
2: Smith SM, Baskin GB, Marx PA Estrogen protects against vaginal transmission of simian immunodeficiency virus. J Infect Dis 2000;182: 708- 15.
3: Marx PA, Spira AI, Gettie A, Dailey PJ, Veazey RS, Lackner AA, Mahoney CJ, Miller CJ, Claypool LE, Ho DD, Alexander NJ Progesterone implants enhance SIV vaginal transmission and early virus load. Nat Med 1996; 2: 1084-9.
4: Temmerman M, Nyong'o AO, Bwayo J, Fransen K, Coppens M, Piot P Risk factors for mother-to-child transmission of human immunodeficiency virus-1 infection. Am J Obstet Gynecol 1995; 172: 700-5.
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