Elevated cytokine and chemokine levels in the placenta are associated with in-utero HIV-1 mother-to-child transmission.
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).


METHODS
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 log(10) increase in placental IP-10 was associated with a three-fold increase in the prevalence of in-utero HIV-1 MTCT.


CONCLUSIONS
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.
The Center for Microbial Interface Biology, College of Public Health, The Ohio State University, Columbus, USA.
Surender B
SB
Kumar
Cara E
CE
Rice
Danny A
DA
Milner
Nilsa C
NC
Ramirez
William E
WE
Ackerman
Victor
V
Mwapasa
Abigail Norris
AN
Turner
Jesse J
JJ
Kwiek
D000328:Adult; D016022:Case-Control Studies; D018925:Chemokines / Q000032:analysis / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D012367:RNA, Viral; D055815:Young Adult
D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D012367:RNA, Viral