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.

Design: Prospective study.

Setting: Outpatient clinic.

Patient(s): Healthy nullipara at 30 weeks' amenorrhea and healthy nonpregnant women in their follicular phase.

Intervention (s): 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.

Main Outcome Measure(s): Percentage NK cells, helper lymphocytes, and cytotoxic lymphocytes that were producing IFN-gamma, IL-2, IL-4, or IL-10.

Result(s): 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.

Conclusion(s): 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 1 lymphocyte response are shifted away from a type 1 immune response during pregnancy. (Fertil Steril(R) 2002 77:1032-7. 02002 by American Society for Reproductive Medicine).