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

Byline: Stephen J. Fortunato (a)(b), Ramkumar Menon (a)(b), Kenneth F. Swan (a)(b), Salvatore J. Lombardi (a)(b) Abstract: 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 stimulatory factor in the management of preterm labor associated with the presence of inflammatory cytokines. Author Affiliation: (a) Maternal-Fetal Group, The Women's Hospital at Centennial Medical Center Nashville, Tennessee USA (b) Middle Tennessee Perinatal Research, Center, The Women's Hospital at Centennial Medical Center Nashville, Tennessee USA Article Note: (footnote) * Presented at the Sixteenth Annual Meeting of the Society of Perinatal Obstetricians, Kamuela, Hawaii, February 4-10, 1996.