Monocytes Of Women Research Articles

Single-cell RNA sequencing reveals that an imbalance in monocyte subsets rather than changes in gene expression patterns is a feature of postmenopausal osteoporosis.

The role of monocytes in postmenopausal osteoporosis is widely recognized; however, the mechanisms underlying monocyte reprogramming remain unknown. In this study, single-cell RNA sequencing (scRNA-seq) was conducted on CD14+ bone marrow monocytes obtained from 3 postmenopausal women with normal BMD and 3 women with postmenopausal osteoporosis (PMOP). Monocle2 was used to classify the monocytes into 7 distinct clusters. The proportion of cluster 1 significantly decreased in PMOP patients, while the proportion of cluster 7 increased. Further analysis via GSEA, transcription factor activity analysis, and sc-metabolic analysis revealed significant differences between clusters 1 and 7. Cluster 7 exhibited upregulated pathways associated with inflammation, immunity, and osteoclast differentiation, whereas cluster 1 demonstrated the opposite results. Monocle2, TSCAN, VECTOR, and scVelo data indicated that cluster 1 represented the initial subset and that cluster 7 represents one of the terminal subsets. BayesPrism and ssGSEA were employed to analyze the bulk transcriptome data obtained from the GEO database. The observed alterations in the proportions of 1 and 7 were validated and found to have diagnostic significance. CD16 serves as the marker gene for cluster 7, thus leading to an increased proportion of CD16+ monocytes in women with PMOP. Flow cytometry was used to assess the consistency of outcomes with those of the bioinformatic analysis. Subsequently, an additional scRNA-seq analysis was conducted on bone marrow mononuclear cells obtained from 3 patients with PMOP and 3 postmenopausal women with normal BMD. The differential proportions of cluster 1 and cluster 7 were once again confirmed, with the pathological effect of cluster 7 may attribute to cell-cell communication. The scRNA-seq findings suggest that an imbalance in monocyte subsets is a characteristic feature of PMOP. These findings elucidate the limitations of utilizing bulk transcriptome data for detecting alterations in monocytes, which may influence novel research inquiries.

Correlation between Blood Monocytes and CSF Tau in Alzheimer's Disease: The Effect of Gender and Cognitive Decline.

Neuroinflammation is one of the main mechanisms contributing to the pathogenesis of Alzheimer's disease (AD), although its key role and the immune cells involved have not yet been identified. Blood monocytes appear to play a role in the clearance of AD-related amyloid-β (Aβ) and tau protein. This retrospective study evaluated a possible correlation between blood monocytes; the concentrations of Aβ, total tau (t-Tau), and phosphorylated tau (p-Tau) in the cerebrospinal fluid (CSF); and cognitive decline assessed according to the Montreal Cognitive Assessment (MoCA). We collected data from 33 patients with AD or mild cognitive impairment (MCI) due to AD (15 men and 18 women) and found, along with a significant reduction in the concentration of blood monocytes in women (p-value = 0.083),significant correlations between the number of blood monocytes and the concentration of t-Tau in CSF (p-value = 0.045) and between blood monocytes and MoCA score (p-value = 0.037). These results confirm the role of blood monocytes in the pathogenesis of AD, provide further evidence of a gender difference in the neuroinflammatory process underlying AD, and show that blood monocyte count may reflect the cognitive impairment of AD patients.

Features of the expression of STAT1 and STAT3 mRNA by monocytes of women with a history of recurrent miscarriage

Features of the expression of STAT1 and STAT3 mRNA by monocytes of women with a history of recurrent miscarriage

Monocytes are increased in pregnancy after gestational hypertensive disease

Monocytes derive from bone marrow and circulate in the blood. They phagocytose, produce cytokines and present antigens. Individual monocyte subsets play distinct roles in the pathogenesis of cardiovascular disease, but their implications in gestational hypertensive disease are unclear. Our objective was to examine the difference in monocyte subsets between pregnant women with or without previous hypertension in pregnancy. Women were enrolled in a prospective observational study in which monoclonal antibodies against cell surface receptors were used to detect monocytes in the peripheral blood by flow cytometry. We compared 17 pregnant women with previous hypertension in pregnancy (Group 1) and 42 pregnant women without previous gestational hypertensive disease (Group 2) with 27 healthy, non-pregnant controls (Group 3). The pregnant women were studied at 13 ± 1 weeks gestation. Monocyte subsets were quantified by flow cytometry: Mon1 (CD14++CD16-CCR2+), Mon2 (CD14++CD16+CCR2+), Mon3 (CD14+CD16+CCR2-), their aggregates with platelets and expression of the surface markers. The groups were well-matched for age, body mass index and ethnicity (P > 0.05 for all). Mon1 counts were higher in women with a history of gestational hypertension or preeclampsia compared to other groups (Group 1 = 441 per µl (376–512); Group 2 = 357 (309–457); Group 3 = 323 (277–397); P < 0.001). Mon3 was higher in both groups of pregnant women compared to non-pregnant controls (Group 1 = 51 (38–62); Group 2 = 38 (29–58); Group 3 = 26 (20–40), P = 0.002). Increased monocytes in women with a previous hypertensive pregnancy generates a hypothesis that these cells may link hypertension in pregnancy, chronic inflammation and future cardiovascular risk.

Abstract 410: Statin Use May Alleviate Coagulation- and Inflammation-associated Gene Expression in Circulating Classical Monocytes in Women With Chronic HIV-1 Infection

During virally-suppressed chronic human immunodeficiency virus (HIV) infection, persistent inflammation contributes to the development of cardiovascular disease, a major comorbidity in people living with HIV. Monocytes play a key role in atherosclerotic plaque development, inflammation, and stability, but their contribution to the CVD under viral suppression in people living with HIV remains unknown. Here, we investigated the transcriptomes of classical (CD14 ++ CD16 - ) blood monocytes from 92 women with and without chronic HIV infection and subclinical cardiovascular disease (sCVD), defined as the presence of focal carotid artery plaque, from the Women's Interagency HIV Study (WIHS). Differential gene expression, based on four two-way comparisons among participant groups (HIV-sCVD-, HIV+sCVD-, HIV-sCVD+, and HIV+sCVD+, 23 subjects each), identified large pro-inflammatory gene signatures for both sCVD and virally-suppressed HIV. These findings were further corroborated by Ingenuity Pathway Analysis. We found that classical monocytes persistently express common CVD-related markers of inflammation, including IL6, IL1β, and IL12B; overlapping with many transcripts identified in sCVD+ participants. In comorbid disease (HIV+sCVD+), those reporting statin use showed dramatically reduced pro-coagulant tissue factor (F3) and tissue factor pathway inhibitor (TFPI and TFPI2) gene expression to a level comparable with healthy participants. Cytokine expression profiles associated with the tissue factor pathway were also modified in participants on statins, suggesting that statins may benefit women with chronic HIV infection by limiting pro-coagulation and inflammation pathways in classical monocytes.

Synthesis of the matrix metalloproteinases and its inhibitors by peripheral blood phagocytes of women with hypertansion disorders

Development of the hypertension disorders in pregnant women is associated with the increase of the functional activity of innate immunity cells. RT-PCR assessment of the MMP-2 and TIMP-1 synthesis by peripheral blood phagocytes showed the significant elevation of the MMP-9 mRNA expression by neutrophils in women with chronic arterial hypertension (CAH) and TIMP-1 and TIMP-2 mRNA expression by monocytes in women with CAH and preeclampsia.

Surface antigen expression on peripheral blood monocytes in women with gynecologic malignancies.

BackgroundOf many specialized blood cells, monocytes are gaining increasing attention for their role in neoplastic disorders. The purpose of the present investigation was to determine the expression of selected peripheral blood monocyte surface antigens in cases of cervical, endometrial, and ovarian cancers. In addition, our aim was to validate the diagnostic value of two artificial coefficients recently proposed for the diagnosis of gynecologic malignancies: Neutrophil to Lymphocyte Ratio (NLR), and Multiplication of Neutrophil and Monocyte Counts (MNM).MethodsWe studied 69 white Caucasian women with histopathologic confirmation of endometrial (N = 42), cervical (N = 13), and ovarian (N = 14) cancers. Reference Group I were women suspected of cancer but histologically nullified (N = 20), and Group II were healthy blood donors (N = 23). Expression of CD11a, CD11b, CD11c, CD16, CD54 (ICAM-1), CD62 L (L-selectin), CD64, and HLA-DR was measured with immunofluorescence in a flow cytometer.ResultsCD54 expression increased by ≥35.6% (p < 0.001) whilst HLA-DR decreased by ≥10.8% (p < 0.001) in all cancer subgroups and Group I as compared to blood donors. A correlation (p < 0.05) between CD54 and CD62 L was stronger in all cancers studied than in healthy subjects. There was no difference in the NLR values between any of these subgroups. Moreover, we observed an increase in MNM parameter in cases of cervical and endometrial cancer and in the Reference Group I.ConclusionsIn the studied gynecologic malignancies, CD54 expression on peripheral blood monocytes is enhanced, indicating a higher transmigrational potential present in such patients, and HLA-DR expression diminished, indicating a decreased readiness of the immune system to recognize foreign antigens. The more pronounced correlation for the expression of CD54 and CD62 L in cancer suggests that monocytes uptake from the bloodstream and their local adhesion increase the pool of tumor-associated macrophages. This study challenged the suggested credibility and usefulness of the artificial parameters of MNM and NLR for the differential diagnosis of gynecologic malignancies.

Medium-dose intravenous immunoglobulin therapy for women with six or more recurrent miscarriages

This study aimed to evaluate changes in natural killer (NK) cell activity and the percentage of monocytes in women with recurrent miscarriage who received medium-dose intravenous immunoglobulin (IVIg) therapy. Fourteen women with a history of six or more recurrent miscarriages of unexplained etiology received 60-g IVIg therapy (20g daily, for three days) during early gestation. NK cell activity in the peripheral blood decreased to 12% one week after therapy compared with before therapy (median, 22%, P<0.001) and the percentage of monocytes increased from 5.2% to 7.5% (P<0.005). Four pregnancies ended in live births of healthy neonates, whereas the other ten pregnancies ended in miscarriages. Excluding one miscarriage with a chromosomal abnormality, the live birth rate was 30.8% (4/13). The rate of reduction of NK cell activity in the success group (−58.8%) tended to be greater than that in the failure group (−14.8%, P=0.057).

Cathepsin B: A cysteine protease associated with HIV-neurocognitive disorders and aging

August 20-22, 2012 C human immunodeficiency virus type one (HIV-1) infection leads to a spectrum of neurological and cognitive abnormalities, known collectively as HIV-associated neurocognitive disorders (HAND). HAND manifest in milder forms during despite effective combination antiretroviral therapy.The pathogenesis of HAND is thought to involve HIV-infected perivascular macrophages and microglia, whose activation leads to the release of pro-inflammatory cytokines and other soluble factors toxic to neurons. One factor that may be involved in macrophage-mediated HIV neurotoxicity is cathepsin B, a member of the cysteine protease family. We recently demonstrated that cathepsin B is upregulated in HIV-1 infected monocyte-derived macrophages (MDM), and secreted in a form that has increased neurotoxic activity in vitro and no longer interacted with its normal inhibitors, cystatin B and cystatin C. We recently observed increased expression of cathepsin B and cystatin B in monocytes of women with cognitive impairment, increased cathepsin B activity in plasma, and decreased cathepsin B activity in the CSF. A study of post-mortem brain tissue suggests that cathepsin B is also upregulated in brains from patients with HAND. We will present recent data related to the mechanisms whereby cathepsin B is dysregulated after HIV infection and how this dysregulation causes neuronal cell damage. This work was supported in part by NIH grants R01-MH08316-01, RCMI-NCRRG12RR03051, SNRP-NINDS-1-U54NS431.

Increased Reactive Oxygen Species and Tumor Necrosis Factor-Alpha Production by Monocytes are Associated with Elevated Levels of Uric Acid in Pre-Eclamptic Women

To evaluate associations between hyperuricemia and increases in production of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) in pre-eclamptic pregnancies. This study investigated serum uric acid levels, monocyte production of TNF-α, superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)), as well as superoxide dismutase (SOD) and catalase (CAT) activities in erythrocytes from 30 women with pre-eclampsia (PE) compared with 30 normotensive (NT) pregnant women in the last trimester of pregnancy. Serum uric acid levels (6.1 versus 2.8 mg/dL) as well as endogenous O(2)(-) (2.2 versus 1.6 nm), H(2)O(2) (1.8 versus 1.4 nm) and TNF-α (91.6 versus 40.4 pg/mL) released from monocytes were significantly higher in the pre-eclamptic group than in the NT group (P < 0.05). SOD activity in erythrocytes was also significantly elevated in the PE group (5969.2 versus 4834.7 U/g Hb). No significant difference between groups was observed in relation to CAT activity. Elevated serum uric acid levels are correlated with higher O(2)(-) and TNF-α production by monocytes in women with PE. This may contribute to the enhanced oxidative and inflammatory state characteristic of this disorder.

Leukocytes of pregnant women with small-for-gestational age neonates have a different phenotypic and metabolic activity from those of women with preeclampsia

Objective. Preeclampsia and pregnancies complicated by small-for-gestational age (SGA) neonates share several underlying mechanisms of disease. However, while an exaggerated systemic maternal inflammatory response is regarded as one of the hallmarks of the pathogenesis of preeclampsia, the presence of a similar systemic intra-vascular inflammation in mothers of SGA neonates without hypertension is controversial. The aim of this study was to determine phenotypic and metabolic changes in granulocytes and monocytes of women who develop preeclampsia and those who deliver an SGA neonate, compared to normal pregnant women.Methods. This cross-sectional study included patients with a normal pregnancy (n = 33), preeclampsia (n = 33), and an SGA without preeclampsia (n = 33), matched for gestational age at blood sample collection. Granulocyte and monocyte phenotypes were determined by flow cytometry, using monoclonal antibodies against selective cluster of differentiation (CD) antigens. The panel of antibodies included the following: CD11b, CD14, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were assessed at the basal state and after stimulation (oxidative burst). Results were reported as mean channel brightness (MCB) or intensity of detected fluorescence. Analysis was conducted with non-parametric statistics. A p-value < 0.01 was considered statistically significant.Results. (1) Women who delivered an SGA neonate had a higher MCB of CD11b in granulocytes and monocytes than those with a normal pregnancy (p < 0.001 for both); (2) patients with preeclampsia had a lower median MCB of CD62L in granulocytes (p = 0.006) and a higher median basal iROS and oxidative burst in monocytes than women with an SGA neonate (p = 0.003 and p = 0.002, respectively).Conclusion. Pregnancies complicated by the delivery of an SGA neonate are characterized by a higher activation of maternal peripheral leukocytes than in normal pregnancies, but lower than in pregnancies complicated by preeclampsia.

Antioxidant enzyme dysfunction in monocytes and CSF of Hispanic women with HIV-associated cognitive impairment

HIV-associated cognitive neurological disorders (HAND) prevail in the antiretroviral therapy era. Proteomics analysis of CSF revealed expression of Cu/Zn superoxide dismutase (Cu/Zn SOD) in Hispanic women with cognitive impairment (CI). We tested the hypothesis that there is reduced capacity of antioxidant enzymes in CI by measures of expression and activity of Cu/Zn SOD, catalase, and Se-glutathione peroxidase in HAND. Our results showed that the function of these antioxidants was decreased in the CSF and monocytes of women with CI. These findings have important implications regarding their possible contribution to oxidative stress and in the diagnosis and therapy for HAND.

Flow Cytometric Evaluation of Intracellular Cytokine Synthesis in Peripheral Mononuclear Cells of Women with Endometriosis

Systemic changes related to cytokine expression levels in women with endometriosis remain a subject of controversy. There are many studies concerning this topic showing differential serum cytokine levels; however, there are limited data presenting cytokine expression at the single-cell level. This study focused on this question by measuring intracellular cytokine staining of activated peripheral CD3+ and CD14+ cells from women with endometriosis (investigative group) compared with those with uterine leiomyoma (control group). Isolated peripheral blood mononuclear cells from women with endometriosis and uterine leiomyoma were stimulated with PMA and ionomycin or with LPS to induce intracellular synthesis of TNF-alpha, IFN-gamma, and IL-8 in subpopulations of CD3+ cells and TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 in CD14+ cells. Comparison of the total groups of patients showed no significant differences in any of the intracellular cytokines investigated in the T cells and monocytes of women with endometriosis compared with controls. When the group of women with endometriosis was divided with regard to severity of disease, a significantly lower percentage of CD3+CD8- lymphocytes stained for IFN-gamma and a significantly higher percentage of CD14+ cells stained for MCP-1 in advanced endometriosis patients compared with the control group were observed. We conclude that peripheral mononuclear cells in women with advanced endometriosis may have differential cytokine synthesis in vitro. These results support the idea that differing immune cell activity measured by intracellular cytokine profiles in women with advanced endometriosis may be more a consequence of the disease than a cause.

490: Effect of intravenous magnesium sulfate on free intracellular calcium and magnesium measured in peripheral blood monocytes of women with preeclampsia

AND MAGNESIUM MEASURED IN PERIPHERAL BLOOD MONOCYTES OF WOMEN WITH PREECLAMPSIA JAY BRINGMAN, CHARLES GIBBS, ROBERT AHOKAS, RISA RAMSEY, SYAMAL BHATTACHARYA, ROBERT EGERMAN, University of Tennessee Health Science Center, Obstetrics and Gynecology, Memphis, Tennessee, University of Tennessee Health Science Center, Memphis, Obstetrics and Gynecology, Memphis, Tennessee, University of Tennessee, Obstetrics and Gynecology, Memphis, Tennessee, University of Tennessee Health Science Center, Memphis, General Surgery, Memphis, Tennessee, University of Tennessee Health Science Center, Department of Obstetrics and Gynecology and Internal Medicine, Memphis, Tennessee OBJECTIVE: Intracellular calcium and magnesium are responsible for many cellular functions, including vascular tone and arterial blood flow as calcium channels are known to be magnesium-dependent. We investigated the potential ameliorative effects of magnesium sulfate in preeclampsia by measuring its effect on intracellular free calcium and magnesium in peripheral blood mononuclear cells (PBMCs) as a surrogate of maternal smooth muscle. STUDY DESIGN: After informed consent was obtained, peripheral blood was obtained before and after magnesium sulfate administration to preeclamptic gravidas. Patients were determined to have preeclampsia by ACOG criteria. After Histopaque isolation of PBMCs, intracellular free calcium and magnesium levels were measured ratiometrically using the fluorescent molecular probes Fura-2 and mag Fura-2, respectively. RESULTS: Six patients were included in the study. Intravenous magnesium sulfate resulted in a significant decrease in free intracellular calcium and a significant increase in free intracellular magnesium levels in PBMCs (p 0.0313, p 0.0126, respectively). CONCLUSION: Magnesium sulfate infusion resulted in a lowering of free intracellular calcium and an elevation in free intracellular magnesium levels in PBMCs. Some of the ameliorative effects of intravenous magnesium sulfate may be produced by alterations in intracellular ionic calcium as either a direct effect on contractile proteins or as a secondary messenger for additional processes.

The effects of leptin on the microbicidal activity of monocytes in humans

The effects of leptin at doses typical of the first and second to third trimesters of pregnancy on the microbicidal activity of monocytes in women were studied. It was found that the hormone modulated the enzymatic activity of neutral proteinases produced by monocytes in different ways: it stimulated the activity of elastase and inhibited the activity of cathepsin G. The study of regulation by leptin of the oxidative potential of monocytes showed that leptin in the investigated doses stimulated the enzymatic activity of myeloperoxidase and did not affect the spontaneous luminol-dependent chemiluminescence of monocytes, whereas the hormone exerted a dose-dependent activating effect on the zymosan-induced production of active oxygen metabolites by monocytes.

Postprandial monocyte activation in response to meals with high and low glycemic loads in overweight women

Background: Recent data show that atherosclerosis is initiated and perpetuated by inflammatory events. Activation of immune cells such as monocytes initiates inflammation, a key step in atherosclerosis.Objective: We hypothesize that a high–glycemic load meal activates inflammatory cells, and that this is mediated by elevated circulating triacylglycerol-rich lipoproteins.Design: Sixteen women [body mass index (in kg/m2): 25.7–29.6], aged 20–48 y, consumed meals with a high or a low glycemic load in a crossover fashion. Blood samples were collected before and up to 8 h after the meals. Samples were measured for glucose, insulin, triacylglycerols, and circulating cytokines, and expression of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) was measured by flow cytometry.Results: At 3.5 h after the test meals, we observed a significant increase in monocytes expressing TNF-α with both high–and low–glycemic load meals. Also, expression of IL-1β in monocytes tended to increase, but the change was not significant. The glycemic load of the meal did not influence circulating cytokines and had only a minimal effect on postprandial triacylglycerol concentrations despite marked postprandial changes in glycemia and circulating insulin concentrations.Conclusions: In the postprandial state, monocytes can be activated by both high–and low–glycemic load meals. The glycemic load of a single meal did not have a significant effect on the degree of activation of the monocytes in women who displayed only a modest increase in circulating triacylglycerols in response to test meals. Future studies should examine the effect of glycemic load in subjects who have a hyperlipemic response to dietary carbohydrate.

Endotoxin-induced cytokine production of monocytes of third-trimester pregnant women compared with women in the follicular phase of the menstrual cycle

Objective: Little is known about the function of the innate immune response during pregnancy. We therefore investigated monocyte cytokine production, as a measure of monocyte function, in pregnant women compared with nonpregnant women. Study Design: Whole blood of women in the follicular phase (day 5-6) and of healthy pregnant women (30 weeks) was collected and stimulated with endotoxin (2 μg/mL). After incubation for 4 hours (37°C, 5% carbon dioxide), red blood cells were lysed and white blood cells were permeabilized, followed by staining with anti-CD14 (fluorescein isothiocyanate labeled) and with phycoerythrin-labeled tumor necrosis factor-α, interleukin-1β, or interleukin-12. The cells were analyzed by flow cytometry after fixation. Results are expressed as a percentage cytokine producing cells after endotoxin stimulation. Statistical analysis was performed with the Mann-Whitney U test (P <.05). Results: Compared with the percentage endotoxin-induced cytokine producing peripheral monocytes in women in the follicular phase, this percentage in pregnancy was decreased for interleukin-12 (mean 6.63 ± 1.34 vs 3.34 ± 0.87, P <.05) and tumor necrosis factor-α (mean 50.20 ± 5.80 vs 31.29 ± 5.57, P >.05). No significant difference was seen in the production of interleukin-1β (mean 58.22 ± 11.09 vs 47.18 ± 7.88, P >.05). Conclusion: The percentage of interleukin-12 and tumor necrosis factor-α producing monocytes is decreased in pregnant women compared with nonpregnant women, suggesting that pregnancy is a proinflammatory state. (Am J Obstet Gynecol 2003;188:1073-7.)

Cytokine secretion is impaired in women with diabetes mellitus.

1. Diabetic women with ASB have lower urinary IL-6 concentrations than non-diabetic bacteriuric controls. 2. Monocytes of women with DM type 1 secrete lower TNF-α after ex-vivo stimulation with LPS than monocytes of women without DM.

Rhythmicity of specific and nonspecific resistance in adult women.

We studied biological rhythms of immunological parameters and absorption and digestive activities of neutrophils and monocytes in women during the menstrual cycle. Circadian rhythms of phagocytosis were evaluated. The phagocytic system was characterized by highest activity during ovulation and early luteal phase of the menstrual cycle accompanied by physiological immunosuppression. It was shown that macrophages determine the spatial and temporal organization of specific and nonspecific resistance in women. We evaluated phases of the menstrual cycle optimal for studying rhythms of the immune system and phagocytosis.

Cytokine secretion is impaired in women with diabetes mellitus

As women with diabetes mellitus (DM) have an increased prevalence of asymptomatic bacteriuria (ASB) and it is known that a correlation exists between the increased prevalence of genitourinary tract infection and impaired cytokine production in women infected with Human Immunodeficiency Virus (HIV), we studied urinary cytokine excretion in diabetic women and compared it with that of nondiabetic controls. To evaluate the cytokine secretion capacity of women with DM, both whole blood and isolated monocytes of women with and without DM were stimulated in vitro with lipopolysaccharide (LPS). Lower urinary interleukin-8 (IL-8) and interleukin-6 (IL-6) concentrations (P = 0.1 and P < 0.001, respectively) were found in diabetic women than in nondiabetic controls. A lower urinary leukocyte cell count correlated with lower urinary IL-8 and IL-6 concentrations (P < 0.05). Lower tumour necrosis factor-alpha (TNF-alpha) and IL-6, but comparable interleukin-10 (IL-10) concentrations were found in whole blood (P < 0.04) and isolated monocytes (P = 0.03) of women with DM type 1 compared to women without DM. Diabetic women with ASB have lower urinary IL-6 concentrations than nondiabetic bacteriuric controls. In addition, monocytes of women with DM type 1 secrete lower pro-inflammatory cytokines after stimulation with LPS than monocytes of women without DM. This is not due to an inhibitory effect of the anti-inflammatory cytokine IL-10. This can have important consequences for both host defense, endothelial cell functioning and atherogenesis.