ABSTRACT
OBJECTIVES: In pregnancy, the placental contribution of cytokines to maternal immunosuppression has been established, however their role in normal maternal blood pressure regulation has not been identified. We investigate the contribution of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) to the vasodilation of early pregnancy in non-human primates. We also sequenced the IL-10 baboon gene and compared it with humans. METHODS: The effect of four different treatments, administered sequentially (semi-random-design) on resting 18h, night time, or hourly mean arterial pressure (MAP) and heart rate (HR) were measured using telemetry. An anti-human IL-10 monoclonal antibody (MAb, 1mg, n=7), anti-TNF-alpha antibody (n=3), a combination of anti-IL-10 and anti-TNF-alpha antibodies (n=5) or saline (n=3) control were administered intravenously to baboons in early pregnancy. Plasma and placental IL-10 concentration was measured before and after injection in all animals. RESULTS: Anti-human IL-10 MAb caused a significant increase in MAP of 2.6+/-0.5mmHg over the 18-h period (p<0.05). Administration of TNF-alpha alone or in combination with IL-10 did not alter MAP. There was 97% sequence homology of IL-10 cDNA between humans and baboons. CONCLUSIONS: IL-10 was shown to regulate the vasodilation of early pregnancy in Papio hamadryas. This partial role of IL-10 in the early BP response of primate pregnancy may be relevant to pathophysiological states of human pregnancy such as preeclampsia.
Subject(s)
Blood Pressure/physiology , Interleukin-10/physiology , Amino Acid Sequence/genetics , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Blood Pressure/drug effects , Cells, Cultured , Creatinine/urine , Endometrium/cytology , Endometrium/drug effects , Endometrium/metabolism , Female , Gene Expression/drug effects , Interleukin-10/genetics , Interleukin-10/immunology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Molecular Sequence Data , Papio hamadryas , Phytohemagglutinins/pharmacology , Placenta/drug effects , Placenta/metabolism , Pregnancy , Proteinuria/urine , Sequence Homology, Amino Acid , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/physiologyABSTRACT
PROBLEM: This study aims to investigate and compare in vitro, immune cell production of the immunosuppresor cytokine interleukin-10 (IL-10) and the proinflammatory cytokine tumor necrosis factor (TNF-alpha) between normal pregnancy (NP) and preeclampsia. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from age-matched patients with preeclampsia and women with a NP (n=3/group) and cultured for 48 hr in the absence and presence of the mitogen phytohaemagluttanin (PHA, 1/100). The concentration of IL-10 and TNF-alpha in the culture medium (CM) was measured by ELISA. RESULTS: Stimulated PBMCs associated with preeclampsia had significantly less IL-10 in the CM compared to NP (347+/-39, preeclampsia vs. 689+/-128, NP; p<0.05) but no difference in TNF-alpha. There was no significant difference in IL-10 or TNF-alpha concentration in the CM of unstimulated PBMCs between preeclampsia and NP. CONCLUSIONS: These findings suggest that under in vitro stimulated conditions preeclampsia is associated with an abnormality characterized by a diminished ability of peripheral immune cells to produce the immunosupressor cytokine interleukin-10.
