Interleukin-10 regulates arterial pressure in early primate pregnancy.
OBJECTIVE
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.
Orange
Stefan
S
Statewide Renal Services, Heart Research Institute, Royal Prince Alfred Hospital and University of Sydney, Australia.
Rasko
John E
JE
Thompson
John F
JF
Vaughan
Janet
J
Olive
Emily
E
Pedler
Michelle
M
Horvath
John S
JS
Hennessy
Annemarie
A
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003404:Creatinine / Q000652:urine; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D048529:Papio hamadryas; D010835:Phytohemagglutinins / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011507:Proteinuria / Q000652:urine; D017386:Sequence Homology, Amino Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003404:Creatinine