Increased T-helper-1-type immunity and decreased T-helper-2-type immunity in patients with preeclampsia.

PROBLEM: To examine whether preeclampsia involves type-1 T-helper (TH1) immune hyperactivity. METHOD OF STUDY: Expression of HLA-DR, a cell-surface marker of activation, was analyzed on CD3+, CD4+, and CD8+ T cells in 15 preeclamptic patients and 15 normal pregnant women using flow cytometry. Additionally, peripheral blood mononuclear cells from preeclamptic patients and normal pregnant women were cultured with or without phytohemagglutinin (PHA) stimulation, and interleukin (IL)-2, IL-4, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha concentrations were determined in the supernatant by immunoassays. RESULTS: HLA-DR antigen was expressed more strongly on CD3+ T cells in preeclamptic patients than in normal subjects. In preeclampsia, HLA-DR was expressed more strongly in CD8+ T cells than in CD4- T cells. More TNF-alpha, IL-2, and IFN-gamma were produced by unstimulated and stimulated cultured peripheral blood mononuclear cells from preeclampsia patients than by those from normal subjects. TNF-alpha/IL-4, IL-2/IL-4, and IFN-gamma/IL-4 ratios were higher in preeclamptic patients than in the normal group. Significant positive correlations were observed between mean blood pressure and concentrations of the Th-1 type cytokines IL-2, IFN-gamma, and TNF-alpha. CONCLUSION: Up-regulation of Th1 responses and down-regulation of Th2 responses occur in preeclampsia.

Enhancement by stem cell factor of interleukin-2 (IL-2)-induced DNA synthesis in human decidual CD16- CD56bright natural killer cells mediated by increased expression of the IL-2 receptor alpha chain.

Extracts of chorionic villous and decidual tissue specimens from women in the early stages of pregnancy contained stem cell factor (SCF), the amount in the latter tissue (246.6+/-119.7 pg/mg protein) being approximately three times that in the former. Immunohistochemical analysis revealed the presence of SCF in the mesenchymal cells of the chorion, the trophoblast, and decidual stromal cells, whereas the SCF receptor, c-kit, was detected in the trophoblast and decidual mononuclear leukocytes but not in decidual stromal cells. Reverse transcription and polymerase chain reaction analysis detected transcripts corresponding to both secretory and membrane-bound types of SCF in chorionic tissue, but only those encoding the secretory type in decidual tissue. Flow cytometric analysis showed that c-kit was expressed on decidual CD16- CD56bright natural killer (NK) cells, CD14+ macrophages, and CD34+ hematopoietic progenitor cells, but not on CD3+ T cells or CD16+ NK cells. Although SCF alone had no effect on DNA synthesis in decidual CD16- CD56bright NK cells, it enhanced the proliferative effect of interleukin-2 (IL-2) at IL-2 concentrations that selectively saturate the high-affinity IL-2 receptor (IL-2R). Flow cytometry of decidual mononuclear leukocytes cultured in the presence of SCF demonstrated that this factor increased the expression of the IL-2Ralpha chain, but not IL-2Rbeta and gamma chain expression on CD16- CD56bright NK cells. Results suggest that SCF produced in the decidua increases the expression of the IL-2Ralpha which is usually present in smaller amounts than other two IL-2R chains on decidual CD16- CD56bright NK cells, and thereby promotes the proliferation of these cells in response to low concentrations of IL-2, resulting in an increase of the high affinity IL-2Rs.

Functional expression on human trophoblasts of interleukin 4 and interleukin 7 receptor complexes with a common gamma chain.

The gamma chain in the high-affinity receptor complex for interleukin 2(IL-2) is used in receptor complexes for IL-4 and IL-7. We examined expression and function of the gamma chain in trophoblast cells. Flow cytometric studies demonstrated that the human placental cell line and choriocarcinoma cell lines expressed the IL-2R gamma chain. None of these cell lines expressed the IL-2R alpha and beta chains, whereas the alpha chains of IL-4R and IL-7R were present. The gamma chain and IL-4R and IL-7R mRNA were detected in human placental trophoblasts by the in situ hybridization method. The release of human chorionic gonadotropin by trophoblasts was accelerated by IL-4 and IL-7 in a concentration-dependent manner. These findings indicate that IL-4 and IL-7 are involved in trophoblast function.

Interleukin 4 (IL-4) blocks the IL-2-induced increased in natural killer activity and DNA synthesis of decidual CD16-CD56bright NK cells by inhibiting expression of the IL-2 receptor alpha, beta, and gamma.

The natural killer (NK) activity and DNA synthesis of decidual CD16-CD56bright NK cells were markedly elevated by treatment with interleukin 2 (IL-2). IL-4 did not affect NK activity or DNA synthesis of decidual CD16-CD56bright NK cells, but inhibited the IL-2-induced NK activity and DNA synthesis in a dose-dependent manner. Flow cytometry of decidual mononuclear cells cultured in IL-2 or IL-4 or both IL-2 and IL-4 demonstrated IL-4 inhibition of the expression of the IL-2 receptor alpha (IL-2R alpha), IL-2R beta, and IL-2R gamma on decidual CD16-CD56bright NK cells. This suggests that IL-4 blocks the IL-2-induced NK activity and DNA synthesis of decidual CD16-CD56bright NK cells by inhibiting the expression of IL-2R alpha, IL-2R beta, and IL-2R gamma.

Expression of the interleukin-2 receptor gamma chain on cord blood mononuclear cells.

Lymphocytes in umbilical cord blood and neonatal peripheral blood have been shown to have less ability in an immune reaction. In our present experimental approach to address this issue, we made use of the cord blood of full-term birth infants to investigate the expression of the interleukin- 2 receptor gamma (IL-2Rgamma) chain that is shared with receptors for IL-4, IL-7, IL-9, and IL-15 as well as IL-2. The gamma chain expression in cord blood lymphocytes was about one-third that in the lymphocytes of adults, whereas no significant difference between cord blood and adult monocytes was observed. A reduced expression of the gamma chain was observed in all of the CD4+ T cells, CD8+ T cells, gamma-delta T cells, B cells, CD16+ natural killer (NK) cells, and CD56(bright) NK cells of the cord blood lymphocytes. The reduced gamma chain expression reached two-thirds of that in adults after 3 days of culture in vitro and in infants 3 days after birth, thus implying that the increase in the gamma chain may significantly contribute to the prevention of neonatal infection.

Detection and localization of interleukin-8 mRNA and protein in human placenta and decidual tissues.

It has been reported that interleukin-8 (IL-8) is secreted from the placental and decidual tissues and that IL-8 levels in the amniotic fluids are significantly elevated by chorioamnionitis or labor pain. The present study was aimed at defining the localization of IL-8 mRNA as well as IL-8 protein at the feto-maternal interface using in situ hybridization and immunohistochemical staining. Both IL-8 mRNA and protein were localized in cytotrophoblast, syncytiotrophoblast and Hofbauer cells of the placenta, decidual stromal cells, decidual lymphocytes and endometrial gland cells. IL-8 secretion from glandular cells has not previously been reported. In addition, we confirmed IL-8 mRNA expression and secretion of IL-8 by an endometrial cancer cell line (Ishikawa) using the reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) methods, respectively.

[The importance of CA125 immunohistochemical staining in patients with ovarian cancer].

UNLABELLED: CA125 has been regarded as a marker for hyperplastic conditions, such as endometriosis or infectious peritonitis. A high serum CA125 level should therefore be carefully evaluated clinically. We measured CA125 levels in sera and ascites as well as the volume of ascites in patients with ovarian cancer, and also performed immunohistochemical staining of their primary tumors for CA125. RESULTS: 1. The tumor positive rate for CA125 was 49% immunohistochemically. 2. In the patients whose tumors were positive for CA125, the serum CA125 level was 3,309 U/ml and the ascitic fluid CA125 level was 23,621 U/ml. In the patients whose tumors were negative for CA125 the serum and ascitic fluid levels of CA125 were 264 U/ml and 1,919 U/ml, respectively. Both serum and ascitic fluid CA125 levels were significantly higher in the CA125-positive tumor group than in the CA125-negative tumor group (t-test: both p < 0.05). 3. In both groups, the serum CA125 level increased with advancing stage. 4. There was a positive correlation between the serum CA125 level and the volume of ascites in both groups. CA125-positive tumor group: Y = 1.02X + 0.38, r = 0.90, r2 = 0.81 (p < 0.0001) CA125-negative tumor group: Y = 0.34X + 1.35, r = 0.51, r2 = 0.26 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin-8 production by CD16-CD56bright natural killer cells in the human early pregnancy decidua.

Decidual CD16-CD56bright natural killer (NK) cells were sorted from the decidual mononuclear cells (MNC) at the early pregnancy using a fluorescence activated cell sortor. The CD16-CD56bright NK cell population occupies a major population in the decidual MNC, in contrast to a very small population (< 1%) in the peripheral blood MNC. These decidual CD16-CD56bright NK cells produced a large amount of IL-8, i. e., mean of 96.7 +/- 19.8 ng/ml in the 24 hr-cultured supernatants without any stimulant, which was comparable to the IL-8 production by LPS-stimulated peripheral blood MNC. Most of the IL-8 was ascribable to the production from decidual CD16-CD56bright NK cells. Intracytoplasmic IL-8 in the decidual CD56bright NK cells was also detected by flow cytometry. RT-PCR methods confirmed IL-8 mRNA expression in this population, while no or very scarce expression of IL-1 alpha and IL-1 beta mRNA was observed. The present study is a first observation revealing that decidual CD16-CD56bright NK cells express IL-8 mRNA and produce IL-8.

Complications associated with CDDP intraperitoneal chemotherapy.

As CDDP-ip is known to affect intraperitoneal tumors directly, and reduce CDDP associated adverse reactions, it has been used not only for ovarian cancer but other intraperitoneal tumors. However ip chemotherapy requires catheter placement at the time of laparotomy. We investigated the complications of catheters as an intraperitoneal administration route. The subjects were 84 patients, 39 with temporary catheters and 45 with an implantable port and catheter system. Twenty-seven percent of the temporary catheter patients experienced complications--infection 8%, inflow obstruction 3%, leakage 5%, extrusion 8%, and severe pain 3%. Furthermore, a total of 22% of patients with an implantable port and catheter system experienced complications--inflow obstruction 9%, infection 2%, leakage 4%, and extrusion 7%. Fortunately, no serious complications were observed at our institutions, and the complication incidence seemed lower compared to that of other institutions.