Motohiko Ichijo

Elevation of amniotic fluid interleukin 6 (IL-6), IL-8 and granulocyte colony stimulating factor (G-CSF) in term and preterm parturition

We determined the levels of inflammatory cytokines such as interleukin 6 (IL-6) granulocyte-colony stimulating factor (G-CSF) and IL-8 in the amniotic fluids from women with premature or term delivery. Cytokines were detectable even in the absence of apparent infection (group 1), but much higher cytokine levels were found in cases of intrauterine infection, particularly in cases of premature delivery (group 2). In cases of term delivery (groups 3-5), all of the cytokine levels showed c. 3- to 4-fold increase during labor pain (group 4) and an 8- to 13-fold increase in the presence of endotoxin (group 5), in comparison with the levels in cases where neither factor was present (group 3). Regarding infection, the cytokine levels were 20- to 30-fold higher in chorioamnionitis-positive premature delivery group (group 2), than in the infection-negative group (group 1). All the cytokines were simultaneously induced in amniotic fluid by labor pain and infection, and a significant positive correlation was observed among these three cytokine levels. In-vitro culture system and immunohistochemical study indicated that the cytokines in the amniotic fluid appeared to originate from trophoblasts and decidual cells. Thus, infection and labor pain may trigger the production of inflammatory cytokines at term as well as premature delivery and the determination of these cytokine levels will be a good indication for the prediction of the presence of intrauterine infection.

Detection of IL-6 in human milk and its involvement in IgA production

A large amount of interleukin-6 (IL-6) was found to be contained in human whey. The concentration of IL-6 in colostrum was significantly higher than that in serum or in milk taken 1 month after parturition. Colostrum contained many more mononuclear cells than late milk. In terms of the proportion of monocytes, T cells and B cells, however, there is no difference between colostrum and late milk. There is a significantly positive correlation between the concentration of IL-6 and the number of mononuclear cells in milk. This demonstrates that IL-6 in whey is derived in part from mononuclear cells. Stimulation of human milk mononuclear cells by Staphylococcus aureus Cowan I in the presence of anti-IL-6 antibody markedly decreased the production of IgA. This suggests that IL-6 contained in milk is closely associated with the local production of IgA in the breast.

Primary infection of Japanese infants with adult T-cell leukaemia-associated retrovirus (ATLV): Evidence for viral transmission from mothers to children

Primary infection with adult T-cell leukemia virus (ATLV) was investigated by follow-up studies on 16 ATLV-seropositive mothers and their breastfed infants in an ATLV-endemic area of Japan. Maternal antibody to ATLV decreased in all the infants, and was detectable in only three of 12 infants tested 6 months after birth. Reappearance of the antibody 9-18 months after birth was observed in only four of the 16 infants. The ATLV-bearing cells in peripheral blood were detected in all 16 mothers after delivery. None of the 16 infants showed ATLV-bearing cells in peripheral or cord blood sampled at birth, or 1, 3 or 6 months after birth. However, virus-bearing cells in the blood became detectable 9-18 months after birth in 13 of the 16 infants. Maternal antibody and virus-bearing cells were never detected in a control group of seven infants of ATLV-seronegative mothers. These findings provide evidence for the high incidence of primary ATLV infection during early infancy among infants born to ATLV-seropositive mothers and suggest maternal viral transmission. Furthermore, samples of breast milk from all 12 seropositive mothers examined contained cell-associated ATLV capable of being transmitted to peripheral leucocytes of neonates. This finding suggests that one of the possible maternal transmission routes of ATLV is via breast milk.

Identification of Macrophage Colony-Stimulating Factor in Human Milk and Mammary Gland Epithelial Cells

ABSTRACT: Human milk contains cellular and soluble host-protective components. Macrophages in human milk constitute a major cellular component in contrast to those in the peripheral blood. We have investigated a mechanism of local expansion of macrophages in human milk. First, biologically active macrophage colony-stimulating factor (M-CSF) was identified in human milk. The maximal concentrations of M-CSF in human milk were 10-to 100-fold higher than those in the serum. The concentrations of M-CSF in the milk had no correlation with those in the serum. M-CSF was immunohistochemically detected in the epithelial cells of the ducts and alveoli of the mammary gland. In situhybridization study confirmed the local synthesis of M-CSF in the mammary gland epithelial cells. A possible role of female sex steroids was discussed in the regulation of M-CSF production by mammary gland epithelial cells.

Expression of Granulocyte Colony-Stimulating Factor and its Receptor at the Fetomaternal Interface in Murine and Human Pregnancy

Granulocyte colony-stimulating factor (G-CSF) is a cytokine which regulates proliferation and differentiation of neutrophilic granulocytes, and its receptor (G-CSF-R) is a member of the hemopoietic growth factor receptor family. We studied the expression of G-CSF and G-CSF-R at the fetomaternal interface in murine and human pregnancy. Immunohistochemical analysis and in situ hybridization indicated that both G-CSF and G-CSF-R are expressed in mouse spongiotrophoblasts and placental labyrinths, and human placental cytotrophoblasts and syncytiotrophoblasts. They were also detected in mouse decidual basalis cells and endometrial epithelial cells, and human decidual stromal cells and endometrial gland cells. These results suggest that G-CSF plays a role in decidual and placental functions by autocrine and paracrine mechanisms.

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.

Bottle-feeding can prevent transmission of htlv-1 from mothers to their babies

Breast-feeding is a major factor in the vertical transmission of human T-lymphotropic virus type I (HTLV-I). We studied whether such transmission may be prevented by bottle-feeding. HTLV-I infection was detected by both HTLV-I antigen and antibody tests. Thirty bottle-fed babies were examined 24 months after birth; only one was found to be HTLV-I antigen-positive. This infection rate was lower than that for breast-fed babies in whom HTLV-I antigen was detected in 24 of the 31 24-month-old babies born to HTLV-I positive mothers in a previous study. These results suggest that most vertical transmission of HTLV-I is attributable to breast-feeding and can be prevented by bottle-feeding.

Human Macrophage Colony-Stimulating Factor Induces the Differentiation of Trophoblast

When human cytotrophoblastic cells in the early stage of pregnancy were cultured in a serum-free medium in the presence of human macrophage colony-stimulating factor (M-CSF), the cytotrophoblastic cells fused and formed a typical syncytiotrophoblast which had a dense distribution of microvilli revealed under an electron microscope. On the other hand, cytotrophoblasts incubated with anti-M-CSF antibody showed hardly any syncytiotrophoblast formation. Following this finding, we studied the differentiation of chorionic cells from the viewpoint of hormone secretion. When cytotrophoblasts were incubated in the presence of M-CSF, the supernatant of the culture showed an increase in human chorionic gonadotropin and human placental lactogen levels in proportion to the concentration of M-CSF added. When cytotrophoblasts were incubated in the presence of anti-M-CSF antibody or anti-fms antibody, human chorionic gonadotropin and human placental lactogen secretion were suppressed. Thus, M-CSF was morphologically and endocrinologically found to induce the differentiation of chorionic cells.

Identification of HTLV‐I Sequence in Cord Blood Mononuclear Cells of Neonates Born to HTLV‐I Antigen/Antibody‐positive Mothers by Polymerase Chain Reaction

We developed a polymerase chain reaction (PCR) method which has high sensitivity and simple technique in order to investigate the presence or absence of human T lymphotropic virus type I (HTLV‐I) provirus in cord blood mononuclear cells of neonates born to HTLV‐I carrier mothers. Out of 40, three subjects were found to contain the HTLV‐I provirus genome. These three subjects remained HTLV‐I sequence‐positive in follow‐up study. On the other hand, when examined by a conventional technique for detection of HTLV‐I‐associated antigen on peripheral mononuclear cells, all 40 neonates were HTLV‐I‐associated antigen‐negative. These results suggest that PCR is more sensitive than the conventional antigen detection method and is useful in early detection of HTLV‐I infection in neonates born to HTLV‐I carriers.

T‐Cell Receptors Are Expressed but Down‐Regulated on Intradecidual T Lymphocytes

PROBLEM: Dietl et al. considered “intradecidual T cell tolerance towards fetal antigens” with their observation that intradecidual T cells lack immunohistochemically detectable amounts of T cell receptor (TCR) molecules while expressing normal amounts of CD3 molecules during early normal pregnancy.