OBJECTIVE:
Our purpose was to study the regulatory effects of
recombinant interleukin-10 on interleukin-6 messenger
ribonucleic acid and protein production by human fetal
membranes.
STUDY DESIGN:
Amniochorionic membranes were
collected from women undergoing elective cesarean section.
Membranes were maintained in an organ explant system and
stimulated with media containing lipopolysaccharide (50 ng/ml)
and various amounts of recombinant interleukin-10 (10, 50, 100
ng/ml). Experiments were conducted in a dose- and
time-dependent manner. Transcription and translation of
interleukin-6 were monitored with quantitative reverse
transcriptase-polymerase chain reaction and enzyme- linked
immunosorbent assay.
RESULTS:
Interleukin-10 stimulation of
amniochorionic membranes in culture produced a dose-dependent
decrease in the production of interleukin-6 messenger ribonucleic
acid and protein. Quantitative polymerase chain reaction was
used to document a decrease in interleukin-6 messenger
ribonucleic acid, which paralleled the decrease in peptide levels
as detected with enzyme-linked immunosorbent assay. The
interleukin-10 effect was present only when tissue was
concurrently stimulated with lipopolysaccharide. Interleukin- 10
inhibition could not be produced in the absence of
lipopolysaccharide stimulation.
CONCLUSIONS:
Addition of
interleukin-10 to culture media leads to transcriptional regulation
of interleukin-6, which results in decreased production of both
messenger ribonucleic acid and protein by human amniochorionic
membranes. The decrease in interleukin-6 is a dose-dependent
effect of interleukin-10. This finding may have important
implications with respect to a possible role for interleukin-10 or
an interleukin-10 stimulatory factor in the management of
preterm labor associated with the presence of inflammatory
cytokines.