Monocytes are primed to produce the Th1 type cytokine IL-12 in normal human pregnancy: an intracellular flow cytometric analysis of peripheral blood mononuclear cells

Abstract

SUMMARYThis paper considers both monocytes and peripheral blood lymphocytes as potential targets for maternal immunological modulation in pregnancy. Peripheral blood mononuclear cells (PBMCs) from nonpregnant and normal pregnant donors were stimulated in vitro , and cytokine production detected intracellularly by flow cytometry. It was found that monocyte production of TNF-a was unaltered in pregnancy, while production of IL-12 was significantly enhanced. In contrast, production of the Th1 type cytokine IFN-g was suppressed in the lymphocyte subsets: CD4 + T helper cells and CD56 + NK cells. Production of the Th2 type cytokine IL-4 in CD4 + cells was not significantly altered in pregnancy. These data suggest that the concept that pregnancy is a 'Th2 phenomenon' cannot be generalized to the function of all aspects of maternal cellular immunity as, paradoxically, circulating monocytes are 'primed' to produce the Th1 cytokine IL-12. Furthermore, these data support the hypothesis that components of maternal innate immunity are activated in normal pregnancy.Keywords human pregnancy interleukin 12 monocytes Th1/Th2

Peripheral Parasitaemia and Its Association With Plasma Cytokines Levels in Malaria-Infected Pregnant Women in Aba, Abia State, Nigeria

“…Granted that this factor is species specific and most common with P. falciparum infection, it is well known that sequestration and adherence of malaria parasite to endothelial cells in tissues such as spleen, brain, kidney and placenta may reduce the parasite load in the peripheral circulation (Ockenhause et al, 1992;Newbold et al, 1999;Beeson et al, 2000). The finding presented herein agrees with earlier studies that malaria induces immune stimulation (Inigo and Manuel, 2002;Sacks et al, 2003), resulting in increased secretion of cytokines. Phagocytosis of the parasite or the haemozoin, glycosilphosphatidylinositol (GPI) and the parasite toxin also causes immune stimulation evinced by up-regulation of cytokines (Venugopal, 2007;D'Ombrain et al, 2008).…”

“…The results observed in this study also agrees with the fact that pregnancy is considered to be a state of controlled maternal mild inflammation where levels of pro-inflammatory and regulatory cytokines are raised compared to non-pregnant states as suggested by (Szoba et al, 2003). Data obtained in this study is similar to that obtained by Sacks et al (2003), where the cytokine levels were higher in the pregnant compared to the non-pregnant subjects. The cytokines in the plasma or serum initially are predominantly type-1 because circulating monocytes are primed to produce Th1 cytokines crucial in immune-surveillance against pathogens (Szoba et al 2003).…”

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

“…However, our own data demonstrate different responses based on the stimulation condition: the increase in MIP-1β production was observed only after infection of PBMC cultures with pH1N1 virus, and less so with H3N2 virus, but not with generalized stimulation with PMA/I. This difference is a critical distinction because nearly all in vitro evidence reporting decreased NK-and T-cell function during pregnancy has relied on such nonspecific stimulation (15,16), which our data also demonstrate. The inflammatory response to pH1N1 and H3N2 virus was also very different, with higher frequencies of IFN-γ-producing cells after H3N2 infection but lower T-cell production of MIP-1β.…”

“…For instance, suppression of T-cell and natural killer (NK)-cell responses by regulatory T cells during pregnancy is linked to amelioration of certain autoimmune diseases (10)(11)(12). In addition, NK and T cells from pregnant women exhibit decreased interferon (IFN)-γ and macrophage inflammatory protein (MIP)-1β production in response to interleukin (IL)-12/15 stimulation or phorbol 12-myristate 13-acetate and ionomycin (PMA/I) (13)(14)(15)(16). Prior work has also suggested a systemic type 2 T helper (Th2) bias as pregnancy progresses (17,18).…”

Pro- and antiinflammatory cytokines in threatened miscarriages

“…Most other studies include women who had already miscarried. [66][67][68] In contrast to what previous investigators have carried out, where experiments were done on cultured peripheral blood mononuclear cells, 69,70 fluorescent antibody-labeled whole blood was analyzed by flow cytometry in this case. In view of the patient groups that were recruited (pregnant women who were experiencing vaginal bleeding in the first trimester), we aimed to sample smaller volumes of blood (1 mL) for the entire experiment (100 L/cytokine or receptor), compared with a minimum of 50 mL in the peripheral blood mononuclear cell culture experiments.…”