Determination of cytokine and growth factor levels to assess endothelial dysfunction in reproductive pathologies

Abstract

Our objective was to evaluate the level of cytokines and growth factors in peripheral blood in women with pregnancy failure, including women with detectable antiphospholipid antibodies (APhA). Eighty-eight women aged 22 to 45 years were examined. The patients were divided into groups: control group included women with physiologically normal pregnancy; the main group consisted of women with a history of one or more cases of miscarriage. The main group was subdivided into subgroups depending on the presence or absence of APhA in blood serum. The APhA-positive subgroup and a history of miscarriage was then subdivided into subgroups with high and low levels as measured by ELISA test. We evaluated the levels of antibodies to cardiolipin and beta2-glycoprotein-I, and the concentrations of cytokines (IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17, Eotaxin, bFGF, G-CSF, GM-CSF, IFNg, IP-10, MCP-1 (MCAF), MIP-1a, PDGF-BB, MIP-1b, RANTES, TNFa, VEGF) in their blood serum and plasma samples. Women with a history of miscarriage, either negative or positive for APhA, are at risk, having an increased contents of proinflammatory cytokines in peripheral blood. Moreover, the women with APhA and a history of miscarriage comprise a group at risk for developing preeclampsia, having increased VEGF, IL-6 and IL-8 levels in peripheral blood. AFAs, regardless of their level, may contribute to development of the pathological process, since an imbalance of proand anti-inflammatory cytokines has been shown in women with APhA, due to a decrease in compensatory anti-inflammatory response. Women with a history of miscarriage and AFAs are more susceptible to placental disorders. Determination of a complex of immunological markers enabled us to clarify various pathophysiological pathways of obstetric pathology, including miscarriage of pregnancy. In this regard, the promising approach would be a search for the most significant combinations of proand anti-inflammatory cytokines, growth-promoting and angiogenic factors with both positive and negative regulation.

Keywords

• antiphospholipid antibodies
• circulating
• endothelial dysfunction
• cytokines
• recurrent miscarriage