Kikuchi-Fujimoto disease during early pregnancy.

Kikuchi-Fujimoto disease (KFD) is rare during pregnancy. It is characterized by necrotizing lymphadenitis and often occurs in young Asian women. We report a case of KFD during pregnancy, which was difficult to diagnose. A 37-year-old pregnant female (gestational week [GW] 7+5) was admitted to our hospital because of hyperemesis gravidarum. On the eighth day of hospitalization (GW 8+6), she suddenly developed a fever (38.0°C) with skin rash and posterior pharynx redness. Blood tests showed pancytopenia and abnormal liver function. The patient was misdiagnosed with severe Epstein-Barr virus infection and administered with prednisolone. Subsequently, cervical lymphadenopathy was observed, and biopsy results led to the diagnosis of KFD. Thereafter, her symptoms improved, and she was discharged at GW 13+4. KFD must be included as a differential diagnosis for patients with fever, abnormal liver function, and pancytopenia during pregnancy.

Pathological roles of antimicrobial peptides and pro-inflammatory factors secreted from the cervical epithelium in Gardnerella vaginalis-abundant vaginal flora in pregnancy.

Bacterial vaginosis due to Gardnerella vaginalis (GV) is one of the main causes of preterm birth. Antimicrobial function of the cervical glands prevents ascending pathogen infection. This study investigated the effect of GV on the cervical gland cells. We examined the correlation between GV and neutrophil elastase in the cervical mucous obtained from pregnant women's clinical samples. Culture supernatants (sup) of GV and Lactobacillus crispatus (LC) were added to human immortalized cervical gland cells (EndoCx). Quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine the effects on the production of antimicrobial peptides (AMPs), secretory leukocyte peptidase inhibitor (SLPI), and Elafin. mRNA microarray analysis revealed the expression profile of GV-exposed EndoCx. Moreover, the antimicrobial activity of Elafin against LC and GV was investigated. In the clinical samples, neutrophil elastase was increased in the GV-positive cervical mucous. In an in vitro assay, RT-qPCR and ELISA showed that GV-sup enhanced the secretion of Elafin, but not SLPI, from EndoCx, whereas LC-sup did not. mRNA microarray assay and ELISA results demonstrated that GV-sup enhanced the proinflammatory pathway and interleukin (IL)- 8 secretion from EndoCx as well as cell adhesion and tight junction pathways. Moreover, GV-sup directly enhanced Elafin and IL-8 secretion from the cervical gland cells. In the GV-abundant vaginal flora, IL-8 level increased the neutrophil elastase activity and Elafin inhibited the elastase activity to protect from tissue damage and infection. Thus, the balance of IL-8-induced neutrophil and Elafin-induced antiprotease activities may be crucial in preterm labor.

Reconstructed uterine length is critical for the prevention of cervical stenosis following abdominal trachelectomy in cervical cancer patients.

AIM: Although the procedure of abdominal trachelectomy has been remarkably improved, preventing subsequent cervical stenosis remains challenging. In this study, we analyzed the clinicopathological risk factors for cervical stenosis to explore the appropriate surgical procedures for the prevention of cervical stenosis following trachelectomy. METHODS: Thirty-two patients who underwent abdominal extended and radical trachelectomy were assessed retrospectively (median follow-up period = 33 months). To evaluate the risk factors, the clinicopathological factors were analyzed by univariate and multivariate analyses. The reconstructed uterine length (UtL), that is, the length between the vaginal end of the neo-cervix and the uterine fundus, was measured by transvaginal ultrasound after surgery. The cut-off value for the UtL was assessed by a receiver operating characteristic (ROC) curve analysis. RESULTS: Cervical stenosis of any grade was observed in 12 patients (grade 1 = 9, grade 3b = 3). Among the various clinicopathological factors, the UtL and cervical length (CL) were significantly related to cervical stenosis following trachelectomy. The multivariate analysis revealed that the UtL, but not CL, is an independent risk factor for stenosis. The ROC curve analysis revealed that stenosis was significantly more likely to occur in patients with a UtL shorter than 53 mm (area under the ROC curve = 0.902). UtL in the patients who became pregnant was longer than that in the patients who did not. No evidence of recurrent cancer was observed during the follow-up period. CONCLUSION: Our proposed method may provide a functional reconstructed uterus with preserving fertility by remaining UtL more than 53 mm.

Natural Cytotoxicity Receptors in Decidua Natural Killer Cells of Term Normal Pregnancy.

AIM: To investigate the changes in the maternal immune system at term pregnancy, we studied the expression of natural cytotoxicity receptors (NCRs) and the cytokine production of NK cells in term placenta decidua and peripheral blood. METHODS: Term decidua and peripheral blood were taken from patients undergoing elective cesarean section. The lymphocytes were separated using density gradient centrifugation (DGC) from peripheral blood and were separated from decidua using DGC after enzyme digestion. These cells were stained with FITC anti-CD56 and Per-CP anti-CD3 monoclonal antibodies, and the NCRs were stained with PE-conjugated anti-NKG2D, NKp46, NKp30, and NKp44 monoclonal antibodies. Cytokines, including IFN-γ, TNF-α, IL-10, and TGF-ß, were stained and then analyzed by flow cytometry. RESULTS: There were fewer cells positive for NKG2D, NKp46, and NKp30 among CD56+CD3- cells in deciduas than in peripheral blood, but the percentages of NKp44-positive cells in CD56+CD3- lymphocytes in deciduas tended to be higher. CONCLUSION: The decreased expression of some NCRs in deciduas may be related to decreased cytotoxicity at term pregnancy, but the increased expression of NKp44 may affect the increased cytokine production in the decidua. Similarly, the expression of NCRs in the decidua may be connected to the maintenance of pregnancy at term.

The Expression of MAS1, an Angiotensin (1-7) Receptor, in the Eutopic Proliferative Endometria of Endometriosis Patients.

BACKGROUND/AIM: We demonstrated that AT1 and AT2 are expressed and both pathways balance the renin-angiotensin system in endometriosis. MAS1, a specific receptor of angiotensin (1-7), opposes AT1 pathway-associated tissue remodelling. It is not known whether MAS1 has an effect on the pathogenesis of endometriosis or not. MATERIALS AND METHODS: Ovarian endometriotic tissues (endo-Ov) and eutopic endometrial tissues (endo-Em) were obtained from 29 patients with endometrial cysts. Normal endometrial tissues (cont-Em) were obtained from patients without endometriosis. Immunohistochemical staining was performed for MAS1, AT1 and AT2 in the endometriosis-associated tissues. The mRNA levels of these receptors were examined by quantitative reverse transcription PCR. RESULTS: MAS1 was immune-positive at the apical side of the glandular epithelium in the endometriotic lesions. The MAS1 mRNA levels in endo-Ov were increased significantly, irrespective of the menstrual cycle phase. The MAS1 mRNA levels were significantly higher in the proliferative-tissues of the endometriosis patients than in those of the controls. The ratio of the MAS1 to the AT1 mRNA in the proliferative tissues was increased predominantly in the endometriosis patients compared with that in the controls. CONCLUSION: High MAS1 expression in the endometrium might promote the initiation of endometriosis via migration of proliferative tissue.

Expression of Angiotensin II Types 1 and 2 Receptors in Endometriotic Lesions.

BACKGROUND/AIM: The aim of this study was to evaluate the gene and protein expression of angiotensin type (AT) 1, AT2 receptors in endometriotic lesions and its relation to prostaglandin (PG) synthases. MATERIALS AND METHODS: Endometriosis samples were obtained from 32 patients with endometriotic cysts. Endometrial tissues were obtained during operations for benign gynecological conditions. The expression of the AT1 and AT2 receptor mRNA and that of PG-endoperoxide synthase 2 and microsomal PGE2 synthase-1 (mPGES-1) was examined by quantitative RT-PCR. Immunohistochemical staining was performed for these receptors. RESULTS: AT1 and AT2 receptor proteins were mostly located in endometrial glandular epithelium and some stromal cells. Immunoreactivity of the receptor proteins was observed in both the eutopic endometrium and endometriotic lesions. The AT1/AT2 ratio in endometriotic cysts (median 7.29, range 1.88-187.60) was significantly increased compared with that in the eutopic endometrium in the proliferative-phase in controls (median 1.01, range 0.37-2.09, p < 0.001). There was a relationship between the AT1 mRNA expression and that of mPGES-1 mRNA in the endometriotic cysts (r = 0.394089, p < 0.05). There was a significant relationship between the mRNA expression of the AT2 receptor and that of mPGES-1 in eutopic endometrium of non-endometriotic control (r = 0.610714, p < 0.05). CONCLUSION: Renin-angiotensin system may play an important role in the pathophysiology of endometriosis.

Effects of Cytokines and TLR Ligands on the Production of PlGF and sVEGFR1 in Primary Trophoblasts.

AIM: Cytokines such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) play an important role in maintaining pregnancy. Toll-like receptors (TLRs) have also been associated with innate immune responses during pregnancy. Placenta growth factor (PlGF) is one of the angiogenic factors and soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is one of the antiangiogenic factors that regulate PlGF function. To elucidate the effects of cytokines and TLR ligands on the production of angiogenic and antiangiogenic factors in trophoblasts, we examined the production of PlGF and sVEGFR1 from trophoblasts following stimulation with cytokines and TLR ligands. METHODS: Villous tissues were obtained from healthy pregnant women who had had an artificial abortion. The trophoblasts were isolated from villous tissues. Subsequently, trophoblasts were treated with TNF-α, IFN-γ and TLR ligands. The levels of PlGF and sVEGFR1 were measured by enzyme-linked immunosorbent assay. The expression of those mRNA was analyzed using quantitative reverse transcription PCR. RESULTS: The production of PlGF in trophoblasts increased by the addition of TNF-α or IFN-γ and decreased by TLR4 ligand. sVEGFR1 levels also increased by following the stimulation with IFN-γ or TLR ligand. CONCLUSIONS: Cytokines such as TNF-α and IFN-γ and TLR ligands may contribute to the production of angiogenic and antiangiogenic factors and may affect the placental formation.

Effects of anti-ß2-GPI antibodies on cytokine production in normal first-trimester trophoblast cells.

AIM: The anti-ß2-GPI antibody (aß2-GPIAb) has been detected in recurrent fetal loss with strong pathogenic activity. The effects of aß2-GPIAb on cytokine production and aß2-GPIAb binding sites in first-trimester trophoblast cells were evaluated. METHODS: First-trimester trophoblast cells were cultured in 24-well tissue culture plates with immunoglobulin G (IgG) obtained from aß2-GPIAb-positive and aß2-GPIAb-negative serum. Cytokines in the cultured supernatant were measured using the suspension array system and enzyme-linked immunosorbent assays. To identify potential binding sites for aß2-GPIAb, such as toll-like receptors (TLR) 2 or TLR4, we used mouse monoclonal anti-TLR2 and/or anti-TLR4 antibodies to inhibit TLR and then measured cytokine production. RESULTS: The production of cytokines, such as interleukin-6 and interleukin-8, increased more in response to aß2-GPIAb-positive IgG than to aß2-GPIAb-negative IgG in trophoblast cells. The secretion of cytokines from trophoblast cells decreased when the TLR were blocked with mouse monoclonal anti-TLR2 and anti-TLR4 antibodies. CONCLUSION: We suspect that aß2-GPIAb might increase cytokine production by binding to TLR2 or TLR4. The increased cytokine production in response to aß2-GPIAb might play a role in the increased inflammatory response in the placenta.

Effects of Anti-ß2-Glycoprotein I Antibody on the Expression of Toll-like Receptors mRNA in Choriocarcinoma and Primary Trophoblast Cells.

OBJECTIVE: To investigate the effects of the anti- ß2-glycoprotein I (anti-ß2-GPI) antibody on the tro- phoblast by evaluating the effects of the anti-ß2-GPI antibody on the expression of toll-like receptor (TLR) mRNA in choriocarcinoma cells and primary trophoblast cells. STUDY DESIGN: We cul- tured the choriocarcinoma cells (BeWo) and the pri- mary first trimester tropho- blast with the IgGs taken from anti-ß2-GPI antibody-positive and -negative sera. Four hours later we purified the RNAs from those cells. We measured the expressions of TLR mRNA in cells using real-time. PCR. RESULTS: The expression of TLR mRNA increased in BeWo cells and primary trophoblast cells cultured with the IgGs taken from anti-ß2-GPI antibody-positive women. Specifically, the expression of TLR1, 2, and 4 in BeWo cells -and TLRI, 3, 4, and 9 in first trimester trophoblast cells increased significantly. CONCLUSION: The anti-ß2-GPI antibody-positive IgG increased the TElR mRNA expression in choriocarcino- ma cells and primary trophoblast cells. We suggest that anti-ß2-GPI antibodies may bind to trophoblast and increase the expression of TLR mRNA.

Autoantibodies isolated from patients with preeclampsia induce soluble endoglin production from trophoblast cells via interactions with angiotensin II type 1 receptor.

PROBLEM: This study investigated whether angiotensin II type 1 receptor agonistic autoantibodies (AT1 -AAs) mediate the increased release of soluble endoglin (sEng) in women with preeclampsia. METHOD OF STUDY: Serum samples were obtained from women with normal pregnancies or with preeclampsia. Human first-trimester trophoblast cells were cultured with purified IgG derived from these sera, and the sEng protein and mRNA expression levels were measured in the supernatants. We also determined the effects of the AT1 -AAs on these cells following treatment with an AT1 receptor antagonist (losartan). RESULTS: Compared with the IgG isolated from the women with normal pregnancies, treatments of the preeclamptic patients markedly increased sEng production and mRNA expression in trophoblast cells. Co-treatment with losartan significantly attenuated the release of sEng and sEng mRNA expression in the trophoblast cells. CONCLUSION: AT1 -AAs may be related to the increased release of sEng observed during preeclampsia and may play important roles in the pathology of this disorder.

Expression of placenta growth factor, soluble fms-like tyrosine kinase-1, metal-responsive transcription factor-1, heme oxygenase 1 and hypoxia inducible factor-1α mRNAs in pre-eclampsia placenta and the effect of pre-eclampsia sera on their expression of choriocarcinoma cells.

AIM: We studied the effect of pre-eclampsia sera on the expression of placenta growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), metal-responsive transcription factor-1 (MTF-1), heme oxygenase 1 (HO-1) and hypoxia inducible factor-1α (HIF-1α) mRNAs in JEG-3 cells (trophoblast-derived cells) and placenta from pre-eclampsia patients to investigate pre-eclampsia pathophysiology. MATERIAL AND METHODS: Placenta and serum samples were taken from pre-eclampsia and normal pregnancy patients. JEG-3 cells were cultured with pre-eclampsia and normal pregnant sera in 24-well tissue culture plates. RNA was purified from placental trophoblast cells and JEG-3 cells 24 h after incubation. The expression of mRNA was measured using real-time polymerase chain reaction. RESULTS: The expression of sFlt-1 mRNA increased, and that of PlGF and HO-1 mRNA decreased in JEG-3 cells after incubation with pre-eclampsia sera. The expression of PlGF mRNA decreased, and that of sFlt-1mRNA increased in pre-eclampsia placenta. The expression of MTF-1 and HO-1 mRNA decreased. A correlation was found between PlGF mRNA expression and the expression of MTF-1 and HIF-1α mRNA. A correlation between sFlt-1 and HIF-1α mRNA expression was also found. CONCLUSION: Changes in PlGF mRNA expression in pre-eclampsia placenta may relate to serum factors and the expression of MTF-1 and HIF-α mRNA. Changes in sFlt-1mRNA expression may relate to serum factors and the expression of HIF-α mRNA. We suggest that serum factors play a role in PlGF and sFlt-1 expression in pre-eclampsia placenta.

Successful pregnancy in a case of bladder and ovary endometriosis following cystoscopy-assisted laparoscopic resection.

A 34-year-old, gravida 0 para 0 Japanese woman visited a regional hospital complaining of dysmenorrhea, hematuria during menstruation, and right inguinal pain. She had a history of dysmenorrhea and three prior rounds of in vitro fertilization with embryo transfer, which were all with transfers of cryopreserved-thawed single embryos in natural cycles, resulting in no pregnancy. An ultrasound revealed a large 2 × 1-cm nodule between the bladder and the anterior wall of the uterus and a 3-cm cystic lesion in the right adnexal area. A combined cystoscopic and laparoscopic resection of the bladder endometriosis and cystectomy of the right endometrioma were carried out. A single ultrasound-guided transfer of a cryopreserved-thawed embryo in the cleavage stage was performed 4 months postoperatively, which resulted in an uncomplicated pregnancy. The combined, single procedure was minimally invasive and eradicated the lesions that may have caused the infertility.

Rare case of primary peritoneal pregnancy infiltrated into the Gerota's fascia of the right kidney.

A 33-year-old, gravida 3, para 2, woman was transferred to our hospital, with acute abdominal pain. Abdominal computed tomography (CT) revealed a cystic lesion accompanied by ring-enhancement between the liver and right kidney with fluid collection in the pelvic cavity. Serum hCG value was 3100 mIU/mL. Transvaginal sonography revealed a pseudo-gestational sac in a thickened endometrium. With a preoperative diagnosis of ectopic pregnancy at 7 weeks of gestation, laparotomy was performed. Following careful removal of clots between the liver and right kidney that contained a gestational sac, continuous bleeding from a defect in the Gerota's fascia of the right kidney was noted. The postoperative course was uneventful and the serum hCG concentration decreased markedly. This case demonstrates that the Gerota's fascia is a possible site of ectopic pregnancy, and that CT can identify a pregnancy in the Gerota's fascia as well as in the liver and spleen.

Relationship between Toll-like receptor-4 and mPGES-1 gene expression in local lesions of endometriosis patients.

PROBLEM: Toll-like receptors (TLRs) are innate immune receptors that mediate the pattern recognition of, and response toward, pathogens and host-derived danger signals. We reported that cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase (mPGES) mRNA were expressed in cases of endometriosis. The relationship between COX-2, mPGES-1, and TLR4 in endometriotic lesions has yet to be determined. METHOD OF STUDY: Endometriosis samples were obtained from 37 patients with endometrial cysts. Endometrial tissues were obtained from patients undergoing surgical procedures for benign gynecological conditions. COX-2, mPGES-1, and TLR4 mRNA expressions were examined by real-time quantitative reverse transcription PCR (qRT-PCR) and mPGES-1, and TLR4 protein localization was examined by immunohistochemistry. RESULTS: TLR4 proteins were mostly located to the glandular epithelium. The immunoreactivities of TLR4 and mPGES-1 from endometriosis lesions were significantly higher than those in eutopic endometrium in the proliferative phase. The expression levels of mPGES-1 mRNA in peritoneal endometriosis were higher than those in eutopic endometrium in the proliferative phase. The expression of TLR4 mRNA correlates with that of mPGES-1 mRNA and not with that of COX-2 in endometriotic lesions. CONCLUSION: Relationship between TLR4 and mPGES-1 mRNA in endometriotic lesions indicate that innate immunity may play an important role in the pathogenesis of endometriosis.

Effects of anti-ß2-glycoprotein I antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cell line.

AIM: Anti-ß2-glycoprotein I (anti-ß2-GPI) antibody has been detected in cases of recurrent abortion and intrauterine death. Placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) are growth factors that accelerate villous proliferation. Soluble VEGF receptor-1 (sVEGFR1) is a soluble receptor for PlGF and suppresses the function of PlGF. In order to study the pathological mechanism of anti-ß2-GPI antibody, we evaluated the effects of anti-ß2-GPI antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cells. METHODS: The sera were taken from six anti-ß2-GPI antibody-positive and six anti-ß2-GPI antibody-negative patients with recurrent miscarriages. Choriocarcinoma cells (JEG-3) were cultured in 24-well plates. After each serum and isolated immunoglobulin G (IgG) were added to the culture medium, the PlGF, VEGF and sVEGFR1 in the culture medium were measured by ELISA 24 h later. When the isolated IgG was added to culture medium, only the levels of PlGF were measured. RESULTS: The anti-ß2-GPI antibody-positive sera and isolated IgG significantly suppressed the production of PlGF from JEG-3 cells more strongly than the anti-ß2-GPI antibody-negative sera. The suppressive effects were not changed by serum inactivation. There was no significant difference in the values of the XTT assay and the production of VEGF and sVEGFR1 between the antibody-positive and antibody-negative sera. CONCLUSIONS: Anti-ß2-GPI antibody-positive sera and IgG suppress the production of PlGF from JEG-3 cells. We suggest that the anti-ß2-GPI antibodies may suppress PlGF production from trophoblasts and cause the failure of placenta formation and function.

Paraaortic paraganglioma arising in an ovarian carcinoma patient mimicking lymph node metastasis.

Paragangliomas are rare tumors arising from the chromaffin cells in the autonomic nervous system. While they both occur most frequently along the paraaortic chain, paraganglioma and ovarian carcinoma very rarely occur together. A 61-year-old, post-menopausal woman visited our hospital, with complaints of abdominal pain and genital bleeding. Image analysis showed a 21 x 18 x 10 cm ovarian mass, and a 38 mm tumor at the paraaortic lesion. First, she underwent bilateral salpingo-oophorectomy. Serous papillary cystadenocarcinoma of the left ovary was found, and so a second surgery was performed. The paraaortic tumor was completely eliminated in spite of fluctuating blood pressure intraoperatively. Microscopic examination revealed that the paraaortic tumor was paraganglioma. She was ultimately diagnosed as having ovarian carcinoma stage Ia (FIGO) with coincident paraganglioma. If blood pressure fluctuation is observed during dissection of the paraaortic lymph node, paraganglioma should be suspected and blood pressure must be carefully controlled.

Expression of inducible microsomal prostaglandin E synthase in local lesions of endometriosis patients.

PROBLEM: Recently, an inducible microsomal human prostaglandin E synthase (mPGES) was identified. This enzyme converts the cyclooxygenase (COX) product, prostaglandin (PG) H(2), to PGE(2), an eicosanoid linked to carcinogenesis. Although elevated levels of PGE(2) have been observed in many tumor types including colorectal adenomas and cancers, its role in the pathophysiology of endometriosis is unknown. We previously reported increased expression of COX-2 messenger RNA (mRNA) in local lesions of endometriosis. To further elucidate the mechanism responsible for the elevated levels of PGE(2) in endometriosis, we examined the expression levels of mPGES. METHOD OF STUDY: Samples were obtained from 28 patients, fixed in formalin, and embedded in paraffin for immunohistochemical analysis. We examined the expression of mPGES mRNA in seven cases by reverse transcriptase-polymerase chain reaction using total RNA extracted from frozen samples. RESULTS: Immunohistochemistry revealed increased mPGES immunoreactivity in endometriosis samples compared with eutopic endometria. Microsomal PGES immunoreactivity was observed in both epithelial cells and stromal or inflammatory cells of endometriosis. Increased expression of mPGES-1 mRNA was detected in most of the endometriosis samples. CONCLUSION: Our results suggest that expression of mPGES in addition to COX-2 plays a role in increasing PGE(2) production in endometriosis.

Granulocyte colony-stimulating factor suppresses autologous tumor killing activity of the peripheral blood lymphocytes in the patients with ovarian carcinoma.

PROBLEM: Granulocyte colony-stimulating factor (G-CSF) is often administered to patients with chemotherapy-induced leukocytopenia. However, adequate attention has not been paid to its effects on cancer immunology. Reported by us and others, G-CSF often induces immunosuppression and down-regulation of response T helper (Th)2 directed immune reaction both in vivo and in vitro. In this study, we analyzed the effects of G-CSF on interferon (IFN)-gamma production and autologous tumor killing (ATK) activities of peripheral blood mononuclear cells (PBMCs). METHODS OF STUDY: In order to evaluate the cytokine-induced activation of peripheral T and natural killer (NK) cells, we analyzed IFN-gamma production by interleukin (IL)-2- and IL-12-stimulated PBMCs, using the ELISPOT assay. Specific killing of autologous tumor cells was evaluated by lactate dehydrogenase (LDH) release assay. RESULTS: The PBMC collected from both cancer-bearing patients and healthy subjects showed IL-2- and/or IL-12-induced IFN-gamma production. The frequency of IFN-gamma producing cells was significantly higher in the normal subjects compared with the patients with advanced ovarian carcinoma. The ATK activity was also enhanced in IL-2- and/or IL-12-stimulated PBMCs of patients with ovarian carcinoma. G-CSF almost completely abolished IFN-gamma production and ATK activity of PBMC stimulated with IL-2 and/or IL-12. CONCLUSIONS: The G-CSF appears to be a suppressor of antitumor immunity. Routine administration of G-CSF to cancer patients may not be recommended, except for febrile neutropenia.

Granulocyte colony stimulation factor (G-CSF) suppresses interleukin (IL)-12 and/or IL-2 induced interferon (IFN)-gamma production and cytotoxicity of decidual mononuclear cells.

PROBLEM: The placenta is one of the few non-hematopoietic tissues to express granulocyte colony stimulation factor (G-CSF). Placental G-CSF production is considered to be one of the major causes of granulocytosis during pregnancy although its physiological role in pregnancy has not yet been examined. METHOD OF STUDY: The effects of G-CSF on interleukin (IL)-2 and/or IL-12 induced interferon (IFN)-gamma production of magnetic cell sorting (MACS) sorted decidual lymphocytes was examined by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT). The effect of G-CSF on cytotoxicity of decidual lymphocytes against the choriocarcinoma cell line JEG-3 was examined by lactate dehydrogenase (LDH) release assay. RESULTS: As previously reported by us, IL-2 and/or IL-12 activated decidual mononuclear cells were capable of killing choriocarcinoma cells. We observed that G-CSF abolished IFN-gamma production and cytotoxicity of decidual mononuclear cells and MACS sorted CD56+ cells. CONCLUSIONS: In addition to its well-known trophic effects on hematopoiesis, our results suggest about new roles of G-CSF in reproductive immunology.