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Paired Peripheral Blood and Cervicovaginal Secretion Chemokine Levels in Exposed Uninfected Women: Elevated Levels of Beta but not Alpha Chemokines
Ajay Wanchu*, R Sachdeva, P Suresh, and R Bagga
PGIMER, Chandigarh, India
Background: Chemokines are natural ligands for chemokine
receptors, which can block viral entry by interfering with viral binding with
the receptor. Enhanced production of chemokines may protect some individuals
from getting infected despite repeated exposure (EU) to HIV. Because no information
was available regarding paired levels of chemokines in the blood and cervicovaginal
secretions of EU women, we determined these levels in our EU cohort.
Methods: We studied 10 EU women and 9 apparently
healthy women at the Immunodeficiency Clinic, Post Graduate Institute of Medical Education and
Research (PGIMER), Chandigarh, India. All were negative for HIV
infection by ELISA and PCR. Peripheral blood mononuclear cells were stimulated by
200 µL of p24 antigen (4 µg/mL) in each well and, after 48-hour culture in RPMI,
the culture supernatant was separated for chemokine measurement. Cervicovaginal
samples were obtained by a single cotton-tipped swab that was inserted into the
cervix, gently rotated through 360°, and placed in 4 mL of sterile phosphate
buffered saline. Macrophage inhibitory protein (MIP) 1-a, MIP 1-β, and
stromal-derived factor (SDF)-1 were measured using a commercially available
ELISA. Descriptive statistics were used and p
value < 0.05 was regarded significant.
Results: The mean age of the EU and healthy women was
32.8±5.7 and 30.6±8.7 years, respectively. The mean duration of last sexual
exposure was 50.5±29.5 days among EU. Mean MIP-1a levels in the peripheral
blood were 2630±613 pg/mL and 405±76 among EU and healthy women, respectively (p < 0.01). Mean MIP-1β levels in
the peripheral blood were 1230±462 pg/mL and 313+145 pg/mL, among EU and healthy
women, respectively (p < 0.01).
SDF- levels were 220±77pg/mL and 194±54 pg/mL in EU and healthy women (p not significant). Median MIP-1a levels
among EU and healthy women were 12.5 pg/mL and 0 pg/mL, respectively (p < 0.01). Median MIP-1β levels
among EU and healthy women were 7.5 pg/mL and 0 pg/mL, respectively (p < 0.01 for each group). Median
SDF-1 levels in the 2 groups were 0 pg/mL. There was no correlation between
blood and genital chemokine levels in either group.
Conclusions: Elevated levels of MIP-1a and
MIP-1β in the peripheral blood and cervicovaginal secretions of EU may
have a role in protecting these individuals from getting infected. This could
have implications in vaccine development against HIV infection. The discordance
between the peripheral blood and genital secretions might be accounted for by
the 2 being separate immunological compartments.
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