Cytokine production in natural killer cells and lymphocytes in pregnant women compared with women in the follicular phase of the ovarian cycle.
OBJECTIVE
To test whether peripheral natural killer (NK) cells, helper T cells, and cytotoxic lymphocytes of pregnant women shift from a type 1 cytokine production toward a type 2 cytokine production as compared with these cells in women in the follicular phase.


METHODS
Prospective study.


METHODS
Outpatient clinic.


METHODS
Healthy nullipara at 30 weeks' amenorrhea and healthy nonpregnant women in their follicular phase.


METHODS
Samples of whole blood were stimulated with phorbol myristate acetate (PMA; Sigma Chemical Co., St. Louis, MO) and Ca-ionophore in the presence of monensin (Sigma). Lymphocytes were stained with alpha-CD3, alpha-CD8, and alpha-interferon gamma (IFN-gamma) alpha-interleukin 2 (IL-2), IL-4, or IL-10. Analysis was performed by flow cytometry. Statistical evaluation was done with the Mann-Whitney U test.


METHODS
Percentage NK cells, helper lymphocytes, and cytotoxic lymphocytes that were producing IFN-gamma, IL-2, IL-4, or IL-10.


RESULTS
There is a statistically significant decrease in the percentage of NK cells, and helper and cytotoxic lymphocytes that produced IFN-gamma in pregnant women when compared with women in the follicular phase. There is also a statistically significant decrease in the percentage of helper lymphocytes producing IL-2 in pregnant women compared with nonpregnant women.


CONCLUSIONS
We found a decrease in type 1 cytokine production with no change in type 2 cytokine production after in vitro stimulation of "pregnant" NK cells and lymphocytes as compared with "nonpregnant" NK cells and lymphocytes. We suggest that NK cell and lymphocyte response are shifted away from a type 1 immune response during pregnancy.
Veenstra van Nieuwenhoven
Angélique L
AL
Department of Obstetrics and Gynecology, University Hospital, Groningen, The Netherlands. veenstravannieuwenhoven@freeler.nl
Bouman
Annechien
A
Moes
Henk
H
Heineman
Maas-Jan
MJ
de Leij
Lou F M H
LF
Santema
Job
J
Faas
Marijke M
MM
D000328:Adult; D000568:Amenorrhea / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005498:Follicular Phase / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D016207:Cytokines