Interleukin-10 inhibition of interleukin-6 in human amniochorionic membrane: Transcriptional regulation

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. CONCLUSION: 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 stimulator factor in the management of preterm labor associated with the presence of inflammatory cytokines.