Phenotypic and metabolic characteristics of monocytes and granulocytes in normal pregnancy and maternal infection

OBJECTIVE: Normal pregnancy has been proposed to be a state of physiologic activation of the innate limb of the immune response. Recent studies have c oncluded that normal pregnancy produces inflammatory changes in peripheral blood leukocytes akin to those of sepsis. This unexpected observation has i mplications that are critical to understanding the susceptibility of pregna nt women to sepsis, the pathophysiology of preeclampsia, and the biology of normal pregnancy. This study was designed to examine the phenotypic and me tabolic characteristics of monocytes and granulocytes in normal pregnancy a nd in pregnant patients with acute infection. STUDY DESIGN: A cross-sectional study was conducted that included nonpregna nt women (n = 20), normal pregnant women (n = 57), and pregnant women with a positive blood culture and/or pyelonephritis (n = 16). Phenotypic and met abolic characteristics of monocytes and granulocytes were studied with the use of flow cytometry and monoclonal antibodies against surface markers (CD 11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR). Intrac ellular reactive oxygen species were measured at basal conditions and after stimulation (oxidative burst). The stimulation index (ratio of intracellul ar reactive oxygen species after oxidative burst over basal state) was calc ulated. Nonparametric statistics were used. A probability value of <0.1 was considered statistically significant. RESULTS: Granulocytes from normal pregnant women had a higher median mean c hannel brightness for CD14 and CD64, but lower median mean channel brightne ss for CD16 and HLA-DR than granulocytes of nonpregnant women. Granulocytes of patients with acute infection had a higher median mean channel brightne ss for CD64 and CD66b than granulocytes of normal pregnant women. Monocytes from patients with acute infection had a higher mean channel brightness fo r CD11b, CD16, CD18, CD49d, CD64, and CD66b than monocytes of normal pregna nt women. Baseline intracellular reactive oxygen species, oxidative burst, and stimulation index values were significantly higher in the granulocytes and monocytes of normal pregnant women than in the granulocytes and monocyt es of nonpregnant women. Similarly, baseline intracellular reactive oxygen species, oxidative burst, and stimulation index values were higher in women with acute infections than in normal pregnant women. CONCLUSION: Normal pregnancy was associated with phenotypic and metabolic c hanges of granulocytes and monocytes; pregnant women with acute infection h ad more marked phenotypic and metabolic changes of leukocytes than normal p regnant women. These qualitative differences indicate that the innate limb of the immune response is not maximally activated during normal pregnancy.