Interleukin 10 (IL‐10) expression has been found to be correlated with the extent of malignancy in gliomas. In vitro, IL‐10 increases proliferation and migratory capacity in human glioma cell lines. In this study, we localized the site of IL‐10 synthesis in gliomas to cells of microglial origin. Biopsy specimens from 11 patients with malignant glioma were processed on native tissues and at early cell culture passages (0–4). IL‐10 mRNA was analyzed by RT‐PCR and in situ hybridization. Protein was quantitatively assessed by ELISA in cell culture supernatants, and cells expressing IL‐10 were determined by a combination of immunohistochemistry for CD68 (specific for microglia/macrophage lineage) and IL‐10 in situ hybridization. IL‐10 mRNA decreased from passage 0 to 4 in all samples and was undetectable beyond passage 5. Such downregulation of mRNA leads to a steep decrease of IL‐10 protein in culture supernatants (below detection level, 0.05 ng/ml, beyond passage 1). The combination of in situ hybridization for IL‐10 and CD68 immunostaining revealed that only cells of the microglia/macrophage lineage produced IL‐10 mRNA. Our results identify microglia/macrophage cells as the major source of IL‐10 expression in gliomas which decreases markedly during early passages of primary cultures of human gliomas due to a progressive reduction of microglia/macrophages present. Int. J. Cancer 82:12–16, 1999. © 1999 Wiley‐Liss, Inc.
Epidemiological data provide evidence that disease activity of T cell-mediated, organ-specific autoimmune diseases is reduced during pregnancy. Although there are several experimental animal studies on the effect of pregnancy on the immune system, the situation in humans is less clear. We therefore performed a prospective analysis of cytokine mRNA expression in whole blood by a new on-line reverse transcriptase-polymerase chain reaction technique and of serum hormone levels during pregnancy in healthy women. The control group included age-matched non-pregnant healthy women. Quantitativecytokine mRNA expression revealed significantly reduced IL-18, interferon-gamma (IFN-gamma), and IL-2 mRNA levels in the first and second trimester in pregnancy compared with non-pregnant women. No difference between groups was detected for tumour necrosis factor-alpha (TNF-alpha) mRNA. IL-4 and IL-10 mRNA were detected at low levels in only 20% of pregnant women and were reduced to a statistically significant extent in the second and third trimester compared with the control group. Changes in IL-18 mRNA expression correlated inversely with serum values for human choriogonadotropin (HCG) and IL-10 serum levels correlated with increases in serum 17beta-oestradiol levels. These data indicate immunomodulatory effects of pregnancy at the cytokine level which may be related to the variations in the clinical course of organ-specific, T cell-mediated autoimmune diseases during pregnancy.
Cytomegalovirus (CMV) disease is associated with a high mortality in recipients of an allogeneic stem cell transplant. Apparent differences in biological behaviour have been noted among clinical CMV isolates. By amplifying specific functionally relevant regions of the CMV genome [immediate early (IE) exon 3, glycoprotein B (gB)], a possible association of strain variation and clinical symptoms of infection was analysed in 24 patients. A high number of genome mutations of the IE exon 3 region could be documented translating into amino acid changes of viral isolated of 8 out of 15 patients with symptomatic and 2 out of 9 patients with asymptomatic CMV infection. Identical IE mutations and gB types were observed in isolates from two different sites in 6 patients. gB strain 2 was found to be associated with symptomatic CMV infection (P = 0.03). Thus, apart from host factors viral factors might influence the virus-host interaction in severely immunosuppressed patients.
The study was conducted to evaluate the changes in sperm binding capacity and ultrasound measurements of the internal spermatic vein, after operative repair of a varicocele. In order to clarify the effect of a varicocele on fertility, these changes were correlated to pregnancy achievement. Twelve infertile males with subnormal semen parameters and varicocele, underwent operative repair. Pre-and post-operatively, all had semen analysis, hemizona assay and ultrasound of the internal spermatic veins. The patients were divided into three subgroups according to pregnancy outcome, and the changes in the different evaluation tests after the operation were compared. Sperm concentration and motility improved post-operatively in all three subgroups, whereas the hemizona index and ultrasonographic measurements improved significantly only in the subgroup that achieved early pregnancies (the mean post-operative percentage of normal morphology was significantly higher), compared to the subgroup without pregnancies. Unlike sperm parameters which improve after operative repair of the varicocele, but have no correlation to conception, sperm binding and ultrasound measurements of the internal spermatic veins improve significantly in cases that achieve early pregnancies. The use of these tests, as well as measuring the percentage of normal morphology, are recommended in all cases of infertility-related varicocele.
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