INFLAMMATORY CYTOKINE EXPRESSION IS CORRELATED WITH THE LEVEL OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TRANSCRIPTS IN HIV-INFECTED PLACENTAL TROPHOBLASTIC CELLS

The inflammatory cytokines interleukin-1 beta (IL-1 beta), IL-6, and t umor necrosis factor alpha (TNF-alpha) have been associated with incre ased human immunodeficiency virus (HIV) expression and enhanced lympho cyte adhesion to trophoblastic cells in experimental systems. To deter mine if there is a correlation between the expression of these cytokin es and the levels of HIV transcripts in trophoblasts of term placentas from HIV-infected women, we studied the placentae of 30 HIV-positive and 13 control gravidae. Twenty-three of the HN-positive women receive d zidovudine (ZDV) as prophylaxis against HIV vertical transmission; o nly one of the seven women who did not receive ZDV was a transmitter, for an overall vertical transmission rate of 3.8%. Cytokine production was measured by enzyme-linked immunosorbent assay in the supernatants of trophoblastic cell cultures. Additionally, cytokine transcripts an d HIV gag sequences were determined by a quantitative reverse transcri ption-PCR assay. In general, trophoblastic cells of HIV-positive place ntas expressed significantly higher levels of IL-1 beta, IL-6, and TNF -alpha than those of control placentas. All placentas from HIV-positiv e women expressed HIV gag transcripts at either a low (<156 copies per mu g of total RNA) or a high (>156 copies per mu g of total RNA) leve l. There was a statistically significant positive association between the basal level of TNF-alpha production and the level of HIV gag trans cripts of HIV-positive placental trophoblastic cells, Nevertheless, th ese data, coupled with a low transmission rate, would indicate that so me other factors, perhaps working in concert with cytokines, are neces sary for vertical transmission of HIV from mother to infant.