Blood Mononuclear Cells Of Women Research Articles

Cytokines (TH1 and TH2) in Patients With Advanced Cervical Cancer Undergoing Neoadjuvant Chemoradiation

Host factors are critical in regulating tumor growth, and cytokines that modulate immunological control may be of importance in cervical cancer. To study this, the cytokines were measured in peripheral blood mononuclear cells in women with cervical cancer, before and after neoadjuvant chemoradiation, and assessed their correlation with therapeutic response. Ninety patients with advanced cervical cancer and 90 healthy controls were enrolled, and human papillomavirus status was determined. Cytokines were estimated by enzyme-linked immunosorbent assay in pretreatment samples after chemotherapy, brachyradiation, and after follow-up. Response to therapy was assessed during and after therapy and after 1 and 3 years of follow-up. Pretreatment levels of type 1 cytokines (IL-2 and IFN-gamma) showed significant decrease, whereas type 2 cytokines (IL-4 and IL-10) showed significant increase in patients versus controls. After chemotherapy, a mild increase in type 1 cytokine levels was observed in complete responders versus partial/nonresponders, which became highly significant after completion of therapy and remained significant during follow-up. A slight decrease in type 2 cytokine levels was seen in complete responders versus partial/nonresponders, which remained insignificant for IL-10 even after chemoradiation. This important finding suggests that pretreatment type 1 cytokine levels and the extent of their change during treatment can predict the therapeutic response to neoadjuvant chemoradiation in advanced cervical cancer.

Expression of cytokine genes in blood mononuclear cells in women with pyoinflammatory diseases of adnexa uteri.

Production of interleukin, interferon-gamma, and transforming growth beta(2)-factor mRNA in peripheral blood mononuclear cells was studied in women with pyoinflammatory diseases of adnexa uteri. Predominant expression of Th1 proinflammatory cytokine genes in patients was demonstrated. Production of interleukins 4 and 8 mRNA decreased 200- and 60-fold, respectively, in comparison with that in healthy women. One month and a half after extirpation of fallopian tubes the cytokine production in blood mononuclear cells shifted towards antiinflammatory cytokines, expression of interleukin-8 gene returned to normal, and expression of interleukin-4 gene increased.

Detection of male DNA in the liver of female patients with primary biliary cirrhosis

Background/Aims: Primary biliary cirrhosis is a chronic cholestatic liver disease characterized by progressive inflammatory destruction of bile ducts, with eventual hepatic fibrosis and cirrhosis. Since primary biliary cirrhosis affects predominantly middle-aged women and has pathological similarities to hepatic graft-versus-host-disease, we investigated whether fetal cell microchimerism might be involved in the development of this disease. Methods: The presence of Y-chromosome-specific sequences was analyzed by polymerase chain reaction using peripheral blood mononuclear cells from women with primary biliary cirrhosis ( n=18) and healthy (control) women ( n=18), and by in situ hybridization of liver biopsy sections from women with primary biliary cirrhosis ( n=19) and women with chronic hepatitis C or alcoholic liver disease ( n=20). Results: Male cells were detected in liver biopsy specimens of 8 of 19 patients (42%) with primary biliary cirrhosis. Y-chromosome-containing cells were not seen in any of the liver biopsy specimens from women with chronic hepatitis C or alcoholic liver disease. Male cells were detected in peripheral blood mononuclear cells from one healthy control at a level of 1 male cell per 10 6 female cells, but were not detected in peripheral blood mononuclear cells of women with primary biliary cirrhosis. Conclusions: The presence of male cells in the liver of women with primary biliary cirrhosis raises the possibility that fetal cell microchimerism may be involved in the pathogenesis of this chronic liver disease.

T-helper 1-type immunity to trophoblast in women with recurrent spontaneous abortion

<h3>Objective.</h3> —To test the hypothesis that peripheral blood mononuclear cells in women with unexplained recurrent abortion (URA) produce T-helper 1 (T_H1)—type cytokines in response to trophoblast antigens. <h3>Design.</h3> —Cohort study. <h3>Setting.</h3> —Medical center. <h3>Participants.</h3> —A total of 244 women with URA, 13 reproductively normal parous control women, and 10 men. <h3>Main Outcome Measures.</h3> —Supernatants from trophoblast-activated peripheral blood mononuclear cells from all participants were tested for toxic effects on mouse embryos and by enzyme-linked immunosorbent assay (ELISA) for interferon gamma (IFN-γ). Supernatants from 20 URA patients with embryotoxic activity and IFN-γ, 13 reproductively normal parous women, and 10 men were further tested by ELISA for other T_H1-type cytokines (interleukin-2 [IL-2], tumor necrosis factor—β [TNF-β]), T_H2-type cytokines (IL-4, IL-10), and TNF-α. <h3>Results.</h3> —Embryotoxic activity was detected in supernatants from 160 of 244 URA patients and in none of the controls. Interferon gamma was detected in supernatants from 125 of 244 URA patients and was significantly associated with embryotoxicity (121 of 160 supernatants with embryotoxicity vs four of 84 supernatants without embryotoxicity [<i>P</i>&lt;.001]). Of 20 supernatants from patients chosen for further study, all were positive for TNF-α, 17 for TNF-β, two for IL-10, and one for IL-4. No cytokines were detected in supernatants from unstimulated or red blood cell membrane—activated cells of women with URA. In contrast, trophoblast-activated lymphocyte supernatants from reproductively normal women and men neither were embryotoxic nor contained T_H1-type cytokines, but most contained the T_H2-type cytokine IL-10. Three supernatants from reproductively normal women also contained IL-4. <h3>Conclusion.</h3> —Whereas T_H1-type immunity to trophoblast is associated with URA and may play a role in reproductive failure, T_H2-type immunity may be a natural response to trophoblast contributing to successful pregnancy. (<i>JAMA</i>. 1995;273:1933-1936)

T-Helper 1-Type Immunity to Trophoblast in Women With Recurrent Spontaneous Abortion

To test the hypothesis that peripheral blood mononuclear cells in women with unexplained recurrent abortion (URA) produce T-helper 1 (TH1)-type cytokines in response to trophoblast antigens. Cohort study. Medical center. A total of 244 women with URA, 13 reproductively normal parous control women, and 10 men. Supernatants from trophoblast-activated peripheral blood mononuclear cells from all participants were tested for toxic effects on mouse embryos and by enzyme-linked immunosorbent assay (ELISA) for interferon gamma (IFN-gamma). Supernatants from 20 URA patients with embryotoxic activity and IFN-gamma, 13 reproductively normal parous women, and 10 men were further tested by ELISA for other TH1-type cytokines (interleukin-2 [IL-2], tumor necrosis factor-beta [TNF-beta]), TH2-type cytokines (IL-4, IL-10), and TNF-alpha. Embryotoxic activity was detected in supernatants from 160 of 244 URA patients and in none of the controls. Interferon gamma was detected in supernatants from 125 of 244 URA patients and was significantly associated with embryotoxicity (121 of 160 supernatants with embryotoxicity vs four of 84 supernatants without embryotoxicity [P < .001]). Of 20 supernatants from patients chosen for further study, all were positive for TNF-alpha, 17 for TNF-beta, two for IL-10, and one for IL-4. No cytokines were detected in supernatants from unstimulated or red blood cell membrane-activated cells of women with URA. In contrast, trophoblast-activated lymphocyte supernatants from reproductively normal women and men neither were embryotoxic nor contained TH1-type cytokines, but most contained the TH2-type cytokine IL-10. Three supernatants from reproductively normal women also contained IL-4. Whereas TH1-type immunity to trophoblast is associated with URA and may play a role in reproductive failure, TH2-type immunity may be a natural response to trophoblast contributing to successful pregnancy.

Increased inducibility of inflammatory mediators from peripheral blood mononuclear cells of women with salpingitis

To investigate whether immune system activation may contribute to the tissue damage observed in salpingitis, we isolated peripheral blood mononuclear cells and quantitated production of the monocyte activation products tumor necrosis factor-a, interleukin-1, and interleukin-6. Unstimulated cells from 7 of 20 women with salpingitis spontaneously released tumor necrosis factor at a concentration >2 SD above the mean value produced by cells from 29 healthy donors. Interferon gamma (200 Ulml) further induced production of tumor necrosis factor from mononuclear cells of 11 women with salpingitis. In contrast, production of tumor necrosis factor by each of 23 other patients who lacked laparoscopic or clinical evidence of salpingitis was similar to that of the controls. In a subset of women whose cells were tested for production of other monokines, three of nine women with salpingitis spontaneously released interleukin-1 but none of the others did so. Four of nine patients with salpingitis also produced interleukin-6, but none of the others did so. None of the monokines were detected in serum from any subject. The results suggest that monocytes from women with salpingitis are primed in vivo and produce inflammatory mediators under conditions where monocytes from other women are poorly responsive. This increased monokine inducibility may contribute to the tubal damage that is the hallmark of salpingitis.