TY - JOUR
T1 - Elevated cytokine and chemokine levels in the placenta are associated with in-utero HIV-1 mother-to-child transmission
AU - Kumar, Surender B.
AU - Rice, Cara E.
AU - Milner, Danny A.
AU - Ramirez, Nilsa C.
AU - Ackerman IV, William E.
AU - Mwapasa, Victor
AU - Turner, Abigail Norris
AU - Kwiek, Jesse J.
PY - 2012/3/27
Y1 - 2012/3/27
N2 - OBJECTIVE: To determine whether there is an association between cytokine and chemokine levels in plasma isolated from the placenta and HIV-1 mother-to-child transmission (MTCT). DESIGN: We designed a case-control study of HIV-infected, pregnant women enrolled in the Malaria and HIV in Pregnancy cohort. Participants were recruited in Blantyre, Malawi, from 2000 to 2004. Patients were women whose children were HIV-1 DNA-positive at birth (in-utero MTCT) or HIV-1 DNA-negative at birth and HIV-1 DNA-positive at 6 weeks postpartum (intrapartum MTCT); controls were women whose children were HIV-1 DNA-negative both at birth and 6 weeks postpartum. METHODS: After delivery, blood was isolated from an incision on the basal plate of the placenta. We used a Bio-Plex human cytokine assay (Bio-Rad, Hercules, California USA) to simultaneously quantify 27 cytokines, chemokines and growth factors in placental plasma. HIV-1 RNA copies were quantified with the Roche Amplicor kit. RESULTS: Levels of interleukin (IL) 4, IL-5, IL-6, IL-7, IL-9, eotaxin, IL-1Ra and interferon gamma-induced protein 10 (IP-10) were significantly elevated in placental plasma isolated from cases of in-utero HIV-1 MTCT. In contrast, only granulocyte colony-stimulating factor was elevated in placental plasma isolated from cases of intrapartum MTCT. After adjusting for maternal age, gestational age and peripheral CD4 T-cell count, every log10 increase in placental IP-10 was associated with a three-fold increase in the prevalence of in-utero HIV-1 MTCT. CONCLUSION: Elevated cytokine and chemokine levels in placental plasma were associated with in-utero and not intrapartum MTCT. IP-10, which is both a T-cell chemokine and potentiator of HIV-replication, was robustly and independently associated with prevalent, in-utero MTCT.
AB - OBJECTIVE: To determine whether there is an association between cytokine and chemokine levels in plasma isolated from the placenta and HIV-1 mother-to-child transmission (MTCT). DESIGN: We designed a case-control study of HIV-infected, pregnant women enrolled in the Malaria and HIV in Pregnancy cohort. Participants were recruited in Blantyre, Malawi, from 2000 to 2004. Patients were women whose children were HIV-1 DNA-positive at birth (in-utero MTCT) or HIV-1 DNA-negative at birth and HIV-1 DNA-positive at 6 weeks postpartum (intrapartum MTCT); controls were women whose children were HIV-1 DNA-negative both at birth and 6 weeks postpartum. METHODS: After delivery, blood was isolated from an incision on the basal plate of the placenta. We used a Bio-Plex human cytokine assay (Bio-Rad, Hercules, California USA) to simultaneously quantify 27 cytokines, chemokines and growth factors in placental plasma. HIV-1 RNA copies were quantified with the Roche Amplicor kit. RESULTS: Levels of interleukin (IL) 4, IL-5, IL-6, IL-7, IL-9, eotaxin, IL-1Ra and interferon gamma-induced protein 10 (IP-10) were significantly elevated in placental plasma isolated from cases of in-utero HIV-1 MTCT. In contrast, only granulocyte colony-stimulating factor was elevated in placental plasma isolated from cases of intrapartum MTCT. After adjusting for maternal age, gestational age and peripheral CD4 T-cell count, every log10 increase in placental IP-10 was associated with a three-fold increase in the prevalence of in-utero HIV-1 MTCT. CONCLUSION: Elevated cytokine and chemokine levels in placental plasma were associated with in-utero and not intrapartum MTCT. IP-10, which is both a T-cell chemokine and potentiator of HIV-replication, was robustly and independently associated with prevalent, in-utero MTCT.
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U2 - 10.1097/QAD.0b013e3283519b00
DO - 10.1097/QAD.0b013e3283519b00
M3 - Article
C2 - 22301415
AN - SCOPUS:84862800227
SN - 0269-9370
VL - 26
SP - 685
EP - 694
JO - AIDS
JF - AIDS
IS - 6
ER -