Immunomodulation of cellular cytotoxicity to herpes simplex virus infection in pregnancy by inhibition of eicosanoid metabolism.
In an effort to evaluate the relationships among pregnancy, cellular cytotoxicity and herpes simplex virus (HSV) infection, we conducted a series of experiments investigating: (1) the maternal cellular cytotoxic response to HSV infection as compared with non-pregnant hosts, (2) the influence of both cyclooxygenase and lipoxygenase products on cytotoxicity by selective inhibition of their metabolic pathways, and (3) the potential pregnancy-related differences in immune response to selective inhibition of eicosanoid metabolism. Indomethacin was used for cyclooxygenase blockade and nordihydroguaiaretic acid was used to evaluate lipoxygenase inhibition. In the non-infected animals no differences in cytotoxicity were observed between pregnant (1.5% +/- 0.7%) and non-pregnant (4.6% +/- 2.0%) groups. HSV infection increased cytotoxicity equally in both groups (pregnant: 10.6% +/- 2.0% vs. non-pregnant: 14.2% +/- 3.4%). Indomethacin did not significantly alter cytotoxicity in either the pregnant or the non-pregnant groups compared with controls (12.8% +/- 1.8% vs. 10.6% +/- 2.0% and 14.3% +/- 3.9% vs. 14.2% +/- 3.4%, respectively). In contrast, NDGA elicited a significant reduction in the cytotoxic response in both pregnant and non-pregnant hosts (6.2% +/- 1.1% vs. 10.6% +/- 2.0% and 5.7% +/- 1.1% vs. 14.2% +/- 3.4%, respectively). From our study we conclude that: (1) cytotoxicity is maintained at low levels in the absence of HSV infection, (2) HSV infection induces a significant augmentation in host cellular cytotoxicity, (3) pregnant and non-pregnant cytotoxic responses to HSV infection appear comparable, (4) indomethacin does not augment in vitro cytotoxicity to HSV infection and (5) NDGA suppresses cytotoxicity, providing evidence that lipoxygenase metabolites are essential to cytotoxic cell function.
Feinberg
B B
BB
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Medical School, Houston.
Tan
N S
NS
Donovan
P K
PK
Loftin
K C
KC
Gonik
B
B
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000378:metabolism; D007165:Immunosuppression Therapy / Q000379:methods; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000276:immunology; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000378:metabolism; D011270:Pregnancy, Animal / Q000276:immunology* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000276:immunology
D015777:Eicosanoids; D009637:Masoprocol; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin