A sphingosine-1-phosphate receptor 1 agonist inhibits tertiary lymphoid tissue reactivation and hypersensitivity in the lung.

Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P1) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P1 caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by S1P1-positive microvessels. Upon MSS rechallenge, the S1P1 agonist RP001 prevented the pulmonary increase of CXCL13, a chief regulator of B-cell recruitment in lymphoid tissues. This was associated with a complete inhibition of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS-specific antibody titers in the lung. Interference with TLT reactivation was associated with a 77% reduction of neutrophil accumulation and with full inhibition of protein-rich leakage in the airways. Thus, an S1P1 agonist hinders TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic features of experimental hypersensitivity pneumonitis.

Replacing an inpatient electronic medical record. Lessons learned from user satisfaction with the former system.

OBJECTIVE: Since it is important to develop strategies for the successful implementation of electronic clinical information systems, the aim of this study is to explore where, and to what extent, users' attitudes toward the former system that is being replaced may vary. METHODS: A cross-sectional survey of 346 nurses and physicians practicing in two Canadian teaching hospitals resulted in a total response rate of 63%. User attitudes were measured in three dimensions: a) user satisfaction with the system's quality attributes, b) perceived system usefulness, and c) perceived impact on quality of care and patient safety. The current system (the one being replaced) was analyzed as a dual system composed of both paper-based and electronic records. RESULTS: The results on user satisfaction demonstrate a wide variation in opinions, with satisfaction ranging from 4.2 to 7.7 on a 10-point disagree-agree, Likert scale. The quality attributes varied by record type, with differences that were systematically in favor of the electronic record component, which received higher scores. The results also highlighted large differences by user group. Physicians and nurses systematically rated the two record formats differently. The nurses were more satisfied with the attributes of the paper-based record. Multivariate regression analyses results also revealed strong interdependencies among the three dimensions of user attitudes, to the extent that perceived system usefulness was strongly correlated with system quality attributes and the system outcomes were also correlated, although less strongly, with the two former system dimensions. CONCLUSION: Understanding users' attitudes toward a clinical information system in use, both in its paper and electronic aspects, is crucial for developing more successful implementation strategies for electronic record systems.

[Child tuberculosis at the teaching hospital of Brazzaville from 1995 to 2003]. / La tuberculose chez l'enfant au CHU de Brazzaville de 1995 à 2003.

In the paediatric service of the teaching hospital of Brazzaville, 582 files of children hospitalized were studied from January 1995 to December 2003. To determine tuberculosis frequency among sickle cell children and estimate the clinical and paraclinical aspects, a case-control study of tubercular patients with HIV negative serology was carried out by comparing at the same time a cohort of 75 sickle cell patients versus 125 patients without sickle cell disease. The results of these studies are as follows. The main assessment is the high frequency of tuberculosis. In 1995 the tuberculosis rate reaches 8%, in 2003 it was up to 13.6%, and 20.6% in 2000 due to the serious consequences of the recurrent wars between 1993 and 1999. Another cause of that high frequency is the rate of HIV/aids patients with a frequency of 2.5% of hospitalization ranging from 1.6 to 3.2%, among them 35% of the tubercular patients were seropositive. The tuberculosis prevalence was 7.4% among sickle cell patients versus 14.2% among control patients. Infection was more often identified in control patients (51.2%) than in sickle cell patients (24%). 68% of the parents were really poor and 18.5% of the children were evicted from their home by war. The pulmonary localizations were prevailing in groups of patients with sickle cell disease as well as in group of control patients. Pleuritis was observed in 8% of the patients with sickle cell disease versus 16.8% for control patients (P = 0.02). No patient with sickle cell disease had a miliary. Anergia to tuberculin test was reported in 35.8% sickle cell patients versus 10.4% for the control patients (P = 0.001). Tuberculosis prevalence is higher among control patients than in sickle cell patients. The high proportion of clinical and paraclinical data of tuberculosis did not significantly differ from the two groups. Evolution was good for 98% of the patients, 1.4% of them died; 74% of deceased patients were affected by HIV/aids.

[Tuberculosis and HIV/AIDS co-infection in children: experience carried out in paediatric service of the teaching hospital of Brazzaville, Republic of Congo (1995-2004)]. / Tuberculose et infection dues au VIH/sida chez l'enfant: expérience du service de pédiatrie du CHU de Brazzaville, Congo (1995-2004).

Epidemiologic, clinical and paraclinical data of 126 children with tuberculosis whose HIV status was known, have been compared. Among them, 65% were HIV positive, the co-infection tuberculosis HIV/AIDS was observed in all social categories. The source of contamination was discovered for 72% of the patients. The mother was involved in 47.5% of cases. The main reasons of consultation were a long standing fever a chronic cough and a weight loss. Diarrhea was mainly observed in positive HIV patients (p = 0.00). The general condition was influenced by a weight loss which was more important in positive patients with a IMC lower than 10 in 12.8% of cases. There was no significant difference between all clinical forms. Digital hippocratism, chronic otitis and parotiditis were only observed in positive HIV patients with skin illness ten times more frequent (p = 0.00). Anergia to tuberculin tests (78.4%) and a sedimentation speed up to 100 mm at the first hour were observed in more than 60% of the positive HIV patients (p = 0.001). Evolution was favorable under treatment for 84% of positive HIV patients with an increasing weight becoming weaker after one month of treatment. All deaths happened among that population.

[Recurrent quadric paralysis in an 11-year-old girl with spinal tuberculosis]. / Tétraplégie récidivante chez une enfant de 11 ans présentant un mal de Pott cervical.

The authors report a recurring quadric paralysis in a 11-year-old girl with cervical, pulmonary and mediastinal tuberculosis. The diagnosis was belated. After the first treatment with anti tuberculosis drugs and immobilization with a surgical collar, an improvement has been obtained; but at the 8th month of this treatment, a partial paralysis of superior members and total paralysis of inferior members appeared. A treatment with streptomycin, ethambutol, rifampicin, pyrazinamide, isoniazide, and prednisone was undertaken. The spontaneous motility was observed at 37 days of treatment. However, at the 8th months of this treatment, quadric paralysis happened again after a fall down. After immobilization with a new surgical collar and prednisone, the spontaneous motility came back again 3 months later.

Rosiglitazone and ethinyl estradiol/cyproterone acetate as single and combined treatment of overweight women with polycystic ovary syndrome and insulin resistance.

BACKGROUND: Few studies have evaluated insulin sensitizers in comparison/association with oral contraceptives (OC) in women with polycystic ovary syndrome (PCOS) with insulin resistance (IR). This study assessed the effects of a thiazolidinedione versus an anti-androgenic estrogen-progestin followed by their sequential combinations in overweight PCOS women. METHODS AND RESULTS: Twenty-eight candidates in whom elevated insulin was not normalized after 4 months of diet were randomly assigned to 6 months of rosiglitazone 4 mg/day or to ethinyl estradiol 35 mg/cyproterone acetate 2 mg (EE/CPA: 21/28 days cycle). Each group then received both medications for another 6 months. Rosiglitazone reduced insulin, IR indices [homeostasis model assessment (HOMA) and quantitative sensitivity check index (QUICKI)] and the insulin area under the curve in response to an oral glucose tolerance test (OGTT), but had limited effect on lipids, androgens and hirsutism. EE/CPA did not modify insulin and OGTT response but increased high-density lipoprotein cholesterol and triglycerides and decreased androgens and hirsutism. Similar changes occurred during combined treatments. End results were highly significant in combined groups without noticeable side-effects or changes in safety parameters. CONCLUSIONS: In obese PCOS women with high insulin not corrected by diet, the combination of rosiglitazone and EE/CPA may be used to achieve complementary beneficial effects on endocrine-metabolic anomalies and clinical symptoms.

Electrophysiological and molecular identification of hepatocellular volume-activated K+ channels.

Although K+ channels are essential for hepatocellular function, it is not known which channels are involved in the regulatory volume decrease (RVD) in these cells. We have used a combination of electrophysiological and molecular approaches to describe the potential candidates for these channels. The dialysis of short-term cultured rat hepatocytes with a hypotonic solution containing high K+ and low Cl- concentration caused the slow activation of an outward, time-independent current under whole-cell configuration of the patch electrode voltage clamp. The reversal potential of this current suggested that K+ was the primary charge carrier. The swelling-induced K+ current (IKvol) occurred in the absence of Ca2+ and was inhibited with 1 microM Ca2+ in the pipette solution. The activation of IKvol required both Mg2+ and ATP and an increasing concentration of Mg-ATP from 0.25 through 0.5 to 0.9 mM activated IKvol increasingly faster and to a larger extent. The KCNQ1 inhibitor chromanol 293B reversibly depressed IKvol with an IC50 of 26 microM. RT-PCR detected the expression of members of the KCNQ family from KCNQ1 to KCNQ5 and of the accessory proteins KCNE1 to KCNE3 in the rat hepatocytes, but not KCNQ2 and KCNE2 in human liver. Western blotting showed KCNE3 expression in a plasma membrane-enriched fraction from rat hepatocytes. The results suggest that KCNQ1, probably with KCNE2 or KCNE3 as its accessory unit, provides a significant fraction of IKvol in rat hepatocytes.

The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial.

Phytoestrogens are increasingly incorporated into the diet of menopausal women. However, there are limited data on the efficacy of flaxseed on the consequences of estrogen deficiency in menopausal women. The purpose of the study was to assess the effects of flaxseed incorporation into the diet of healthy menopausal women. One hundred and ninety-nine menopausal women were randomly assigned to consume 40 g flaxseed/d (n = 101) or wheat germ placebo (n = 98) for 12 months. At baseline and at month 12, serum levels of lipids, bone mineral density (BMD), and menopausal symptoms were evaluated. Statistical analysis was performed under the intention to treat principle. Flaxseed reduced serum total (-0.20 +/- 0.51 mmol/liter; P = 0.012) and high-density lipoprotein (-0.08 +/- 0.24 mmol/liter; P = 0.031) cholesterol concentrations compared with wheat germ placebo. BMD did not differ significantly between the two arms. Both flaxseed and wheat germ reduced (P < 0.0001) the severity scores of menopausal symptoms, but no statistical difference was found between the two arms. Our findings suggest that 1-yr incorporation of flaxseed into the diet produced a favorable, but not clinically significant, effect on blood cholesterol and caused no significant change in BMD or symptoms in healthy menopausal women.

[Ovarian torsion revealing an ovarian cavernous hemangioma in a child]. / Torsion de tumeur kystique de l'ovaire chez une adolescente, révélatrice d'un hémangiome caverneux.

The authors report one case of cavernous hemangioma of the left ovary, which was revealed by ovarian torsion. Such benign tumors of the blood vessels are rare in ovaries during childhood. This hemangioma was observed in a 13-year-old patient, who presented with abdominal and pelvic pain and vomiting. The pelvic mass was noted and sonography revealed a cystic tumor. An annexectomia was realized. Histology showed narcotized ovary cells, with an increased number of vascular channels composed of thin walled vessels, whose wall consisted of an endothelium. This aspect evoked a cavernous hemangioma of the ovary.

[AIDS at Central University Hospital of Brazzaville: experience of the "Grands Enfants" pediatric department]. / Le SIDA au CHU de Brazzaville: expérience du service de pédiatrie "Grands enfants".

The epidemiological factors, clinical aspects and short term evolution of children infected by aids were assessed over a period of five years in "Grands Enfants" paediatric service of Brazzaville CHU. The medical reports of 81 patients have been collected, their average age was 9 years old +/- 3.5. The HIV 1 was the only identified virus. 59% of children's parents were divorced, and 7% were single. The infection transmission was vertical in 70% of cases, transfusional in 28% of cases and indeterminate in 1% of cases. The symptoms were: the impairment of body status in 90% of cases, shown by a weight loss in 89% of cases; a long-term fever was observed in 56% of cases and a chronic diarrhoea was noticed in 54% of cases. The lymphadenopathies and digestive Candida were observed in 26% and 36% of cases. 6% of the patients had a psychomotor retardation. The respiratory infections and the diarrhoea were pathologies the most frequently noticed. The associated infections were essentially pulmonary tuberculosis 40% of cases, the otitis, the pneumococcal and cryptococcal meningia 2% of cases. The Burkitt lymphoma and the Kaposi sarcoma were shown in 1% of cases. The evolution was shown by a high mortality due to a dehydration in 59% of cases, a respiratory pathology in 22% of cases and anaemia in 15% of cases. This high mortality points out the problem of the treatment of patients, a problem increased by family poverty.

Resistance of Peanut to Sclerotinia Blight and the Effect of Acibenzolar-S-methyl and Fluazinam on Disease Incidence.

Sclerotinia minor, a soilborne fungal pathogen of peanut, can cause serious yield loss in North Carolina. A field test was implemented to study genotype reaction, and the effect of aciben-zolar-S-methyl (a plant activator) and the fungicide fluazinam on disease incidence. In all, 13 genotypes in 1997 and 12 genotypes in 1998 were evaluated. Three applications of acibenzolar-S-methyl (0.14 kg a.i./ha) or fluazinam (0.58 kg a.i./ha) were made on a calendar-based schedule. Disease ratings were made weekly in 1997 and every other week in 1998. Fluazinam suppressed disease at all sites and increased yield at two of three locations. Acibenzolar-S-methyl had no effect on disease incidence or yield. The advanced breeding line N92056C and cvs. Tam-run 98 (TX 901417) and Perry (N93112C) had moderate to high levels of resistance to S. minorand produced high yields compared with susceptible cv. NC 7. Lines derived from wild species also demonstrated moderate to high levels of resistance relative to NC 7 and represent potential breeding lines.

The use of low dose oral contraceptives for the management of acne.

There is compelling evidence that oral contraceptives (OCs) are effective in the management of mild-moderate acne vulgaris, as well as cumulative evidence that elevated levels of androgens in acne patients, relative to appropriate controls, are an underlying pathophysiological factor in acne. All low dose OCs reduce serum free testosterone (T) to a similar extent, which is contrary to the traditional concept that a patient who has acne should not use an OC containing a progestin with androgenic properties. The efficacy of various OCs to improve acne has been reported in transverse, cohort and comparative studies, and more recently in multicenter, randomized, placebo-controlled trials. Recently, an ultra-low dose OC (Alesse, Wyeth) was shown to effectively reduce non-inflammatory and inflammatory lesions in mild-to-moderate acne, while having a profile of side-effects similar to that of a placebo. Besides its contraceptive efficacy, an ultra-low dose OC represents an attractive alternative as a single or associated medication in the management of acne.

Estrogen/progesterone replacement versus pravastatin and their sequential association in hypercholesterolemic postmenopausal women.

OBJECTIVES: The objectives of this study were to assess serum lipid changes in response to an oral estrogen combined with progesterone (Group A) as compared with pravastatin (Group B) and to evaluate the additive effects of the sequential addition of statin to hormonal replacement therapy (HRT) and of HRT to statin. METHODS: Thirty-seven of 63 hypercholesterolemic menopausal women initially submitted to a 4-month diet were randomised to oral conjugated estrogens (0.625 mg)/micronised progesterone (200 mg) or to pravastatin (40 mg). After 6 months, each group received both medications for another 6 months. RESULTS: Nineteen percent of women corrected their lipids below decision levels with diet alone. Low density lipoprotein-cholesterol (LDL-C) decreased by 8+/-5% with HRT and by 26+/-3% (P<0.001) with the statin. These single medications increased high density lipoprotein-cholesterol (HDL-C) by 13+/-5% (P<0.01) and 11+/-7%, respectively. Combined interventions produced cumulative LDL-C reductions of 40+/-2 and 42+/-3% (P<0.001) and additive HDL-C augmentations of 16+/-4 and 23+/-5% (P<0.01) with proportional changes in apolipoprotein (Apo)B-100 and ApoA-1. These combined effects brought the atherogenic index (C/HDL-C) for Groups A and B, respectively, from a moderate (5.18+/-0.25 and 5.87+/-0.18) to a reduced (3.35+/-0.20 and 3.52+/-0.19) risk category. Triglycerides (TG) which were increased by HRT and decreased by the statin returned to baseline during combined treatments. No changes in diet, physical activity or anthropomorphometric measurements explained the lipid modifications. CONCLUSIONS: In menopausal patients with elevated C not responding to diet, pravastatin was most effective to decrease LDL-C, and oral estrogen-micronised progesterone most effective to increase HDL-C. Marked reduction of the atherogenic index is achieved by sequential combinations of medications resulting from beneficial cumulative effects on both C-LDL and C-HDL.

Cytokine expression by murine DX5+ cells in response to IL-12, IL-18, or the combination of IL-12 and IL-18.

In this study we analyzed the response of DX5+ NK and NK T cells to in vitro stimulation with IL-12 or IL-18. Production of IFN-gamma in response to either IL-12 or IL-18 was dependent upon costimulation with either IL-2 or IL-15. DX5+ splenocytes showed a rapid (6 h) and sustained (6-72 h) accumulation of IFN-gamma transcripts followed by a delayed (12-24 h) up-regulation of IL-10 or IL-13 expression in response to IL-2 + IL-12 or IL-2 + IL-18, respectively. Incubation of DX5+ splenocytes with the combination of IL-2 + IL-12 + IL-18 resulted in up-regulation of IFN-gamma and IL-13 transcripts but down-regulation of IL-10 expression. Furthermore, two distinct populations of cells producing differing amounts of IFN-gamma were observed by intracellular staining after stimulation with IL-2 + IL-12 + IL-18. Last, we demonstrate that DX5+ cells respond to IL-18 independently of IL-12, as cells from both wild-type and IL-12Rbeta2KO mice produce IFN-gamma and IL-13 in response to IL-2 + IL-18.

A randomized, controlled trial of a low-dose contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel for acne treatment.

OBJECTIVE: To evaluate the efficacy of a low-dose oral contraceptive (OC) containing 100 microg of levonorgestrel (LNG) and 20 microg of ethinyl estradiol (EE) compared with placebo for the treatment of moderate acne. DESIGN: Multicenter, randomized, double-blind, placebo-controlled clinical trial. SETTING: Outpatient dermatology clinics. PATIENT(S): Women (> or =14 years old; n = 350) with normal menstrual cycles and moderate acne were randomized to receive LNG/EE or placebo for six cycles. INTERVENTION(S): Twenty microg of EE and 100 microg of LNG. MAIN OUTCOME MEASURE(S): Acne lesion counts and clinician global assessment were performed at baseline and at each cycle. Patient self-assessment was carried out at baseline and at cycles 4 and 6; blood pressure and weight were measured at baseline and at cycles 1, 3, and 6. RESULT(S): Inflammatory, noninflammatory, and total lesion counts at cycle 6 with LNG/EE were significantly lower compared to placebo. Patients in the LNG/EE group also had significantly better clinician global and patient self-assessment scores than those in the placebo group at cycle. Changes in weight from baseline were similar between patients in the LNG/EE and placebo groups at all measured time points. CONCLUSION(S): This double-blind, placebo-controlled study demonstrates that a low-dose OC containing 20 microg of EE and 100 microg of LNG is an effective and safe treatment for moderate acne.

Haptoglobin is present in human endometrium and shows elevated levels in the decidua during pregnancy.

Assuming that haptoglobin, by virtue of its immunomodulatory properties, could be a regulatory factor during reproduction, its presence in the human uterus was determined. Protein extracts from endometrial tissue samples of pregnant and non-pregnant women were analysed by the immunoblot technique and the intensities of specific bands were quantified. Bands corresponding to haptoglobin were identified in tissue samples obtained from both sources. Protein, purified by high-performance liquid chromatography and monitored by Western blot analysis for its haptoglobin identity, was used for amino-terminal sequencing. Sequencing of the 42 kDa protein identified it as the beta chain of haptoglobin. Immunohistochemistry was used to corroborate the findings and to visualize the distribution of haptoglobin in the tissue. The intensity of the 42 kDa band derived from decidua graviditatis was significantly higher than the intensity of bands derived from non-pregnant endometrium in the proliferative phase (P < 0.01) and in the secretory phase (P < 0.05). Immunohistochemical staining with anti-human haptoglobin antibody elicited strong signals in the decidua graviditatis and weaker signals in the normal endometrium, with the latter showing menstrual cycle-dependent variation. Moderate staining of stroma and a lack of staining of epithelium in the proliferative phase contrasted with the strong staining of stroma and moderate level of staining of epithelium observed in the secretory phase. Haptoglobin in the uterus may exert several functions such as the known binding of haemoglobin, but could also be involved in the multi-factorial mechanism protecting the fetus from a maternal allograft-like immune response.

Comparative effect of danazol and a GnRH agonist on monocyte chemotactic protein-1 expression by endometriotic cells.

PROBLEM: Endometriosis is associated with a chronic inflammatory process, and the increased number of activated peritoneal macrophages is one of the major hallmarks of this process. The medical treatment of the disease, which is based on the creation of an hypoestrogenic milieu unfavorable to the growth of endometriotic lesions, is often associated with a reduced peritoneal inflammation. The aim of this study was to investigate the ability of current therapeutic agents to modulate, through a direct mechanism, the expression by endometriotic cells of monocyte chemotactic protein-1 (MCP-1), a chemokine endowed with the potent faculty of recruiting and activating macrophages. METHOD OF STUDY: Cells were stimulated with interleukin-1 beta (IL-1beta) to induce MCP-1 expression. MCP-1 protein secretion and mRNA steady-state levels were evaluated by ELISA and northern blot, respectively. RESULTS: Our results show that danazol concentrations (10(-7) -10(-5) M), taking into account the therapeutic levels found in the plasma of treated patients, inhibited MCP-1 protein and mRNA steady-state levels in endometriotic cells, whereas buserelin acetate (0.1-10 ng/mL), a GnRH agonist, had no significant effect. Dexamethasone, an anti-inflammatory glucocorticoid, used at concentrations varying between 10(-12) and 10(-6) M, also displayed a dose-dependent inhibitory action. CONCLUSIONS: These results put into prominence the capability of danazol to directly inhibit the expression of a potent monocyte chemotactic and activating factor by ectopic endometrial cells shedding more light on the mechanisms underlying the clinical effects of hormonal therapeutic agents used in the treatment of endometriosis.

Effect of hormonal agents on monocyte chemotactic protein-1 expression by endometrial epithelial cells of women with endometriosis.

OBJECTIVE: To assess whether hormonal agents used in the medical treatment of endometriosis, such as danazol and GnRH agonist, exert direct regulatory action on monocyte chemotactic protein-1 (MCP-1) expression by endometrial epithelial cells. DESIGN: Primary cultures of epithelial cells isolated from human endometrium were exposed to different concentrations of cytokines and steroid hormone analogs. Expression of MCP-1 was analyzed at the levels of protein and messenger RNA. SETTING: Gynecology clinic and laboratory of endocrinology of reproduction. PATIENT(S): Women presenting for infertility or pelvic pain in whom endometriosis was diagnosed by using laparoscopy. INTERVENTION(S): Endometrial tissue biopsy performed at laparoscopy. MAIN OUTCOME MEASURE(S): Secretion of MCP-1 protein was measured by using enzyme-linked immunosorbent assay, and mRNA steady-state levels were measured by performing Northern blot analysis. RESULT(S): Buserelin acetate, a GnRH agonist (0.1-10 ng/mL), had no significant effect on MCP-1 expression, whereas danazol (10(-7)-10(-5) M), a testosterone analog, and dexamethasone, an anti-inflammatory glucocorticoid hormone (10(-12)-10(-6)M), showed a direct and a dose-dependent inhibitory effect on MCP-1 expression. This effect occurred at the level of protein and mRNA. CONCLUSION(S): The findings of the study may affect understanding of the mechanisms by which hormonal treatments act on endometriosis and influence its clinical manifestations.

Ovarian hormones modulate monocyte chemotactic protein-1 expression in endometrial cells of women with endometriosis.

Endometriosis, a frequent oestrogen-dependent disease believed to result from an aberrant proliferation of endometrial tissue outside the uterine cavity, is associated with an increased expression of monocyte chemotactic protein-1 (MCP-1) in the intrauterine endometrium. This makes it plausible that migrating endometrial cells are intrinsically able to initiate monocyte chemoattraction and activation, a phenomenon which has been consistently observed in the peritoneal cavity of patients and recently in their eutopic endometrium. To elucidate the mechanisms involved in the regulation of MCP-1 expression in eutopic endometrial cells, we studied the effects of ovarian hormones and found that oestradiol (10(-9) and 10(-8) mol/l) markedly increased MCP-1 mRNA steady-state levels and protein secretion by endometrial cells in response to interleukin-1beta (IL-1beta) (0.1 ng/ml). The IL-1beta-induced MCP-1 expression was even higher following pretreatment of cells with both oestradiol (10(-9) mol/l) and progesterone (5x10(-8) mol/l). This did not seem to be due to increased MCP-1 mRNA stability, but rather to a higher level of gene transcription. Our results provide evidence that ovarian steroids regulate, indirectly, the synthesis and the secretion of a potent chemotactic and activating factor for monocytes/macrophages by endometrial cells of women with endometriosis and reveal a new mechanism for oestradiol action.