B Cell-Activating Factor Enhances Interleukin-6 and Interleukin-10 Production by ODN-Activated Human B Cells

We aim to investigate the additive value of B cell‐activating factor (BAFF) when added to oligodeoxynucleotides (ODN)‐activated B cells with respect to TLR‐9, CD69, MHC‐II expression, IL‐6 and IL‐10 secretion and B cell cycling. Therefore, B cells from healthy individuals were incubated under the following conditions: (1) B cells with medium, (2) B cells with ODN 0.5 μm , (3) B cells with BAFF 20 μm and (4) B cells with both ODN 0.5 μm and BAFF 20 μm . We found that addition of BAFF did not enhance the expression of TLR‐9, CD69 and MHC‐II in ODN‐activated B cells. Incubation of B cells with BAFF and ODN together leads to a marked elevation of IL‐6 and IL‐10 levels compared to ODN alone. Synthesis and mitosis were higher in B cells stimulated by BAFF than in B cells stimulated by ODN. These findings suggest that both BAFF and TLR‐9 contribute independently to B cell function.     

Regulation of Interleukin-6 Expression in Human Decidual Cells and Its Potential Role in Chorioamnionitis

Chorioamnionitis frequently precedes both genital tract and placental inflammation and is both a primary cause of maternal morbidity and a major antecedent of preterm premature rupture of the membranes (PPROM) as well as preterm delivery (PTD). In most cases of chorioamnionitis, neutrophils dominate the decidua. In a subset of these cases, a predominance of monocytes is uniquely associated with both neonatal intraventricular hemorrhage and death. The multifunctional cytokine, interleukin-6, promotes local monocyte dominance via several mechanisms. In this study, immunostaining of placental sections revealed significantly higher interleukin-6 HSCOREs in decidual cells (DCs) but not in interstitial trophoblasts, in chorioamnionitis versus gestational age-matched control placentas (P < 0.05). In confluent leukocyte-free term DCs, secreted interleukin-6 levels in incubations with estradiol-17β were increased 2500-fold by IL-1β (P < 0.05). This up-regulation was inhibited by more than 50% in parallel incubations that included medroxyprogesterone acetate (n = 12, P < 0.05). Western blotting data confirmed these enzyme-linked immunosorbent assay results; quantitative RT-PCR findings demonstrated corresponding changes in interleukin-6 mRNA levels. Specific inhibitors of signaling for both nuclear factor-κB activation and p38-mitogen-activated protein kinase, but not for protein kinase C, significantly decreased IL-1β-enhanced interleukin-6 expression levels in cultured DCs. In conclusion, in situ and in vitro results indicate that significantly enhanced interleukin-6 expression levels in DCs during chorioamnionitis could be pivotal in skewing decidual monocyte differentiation to macrophages.During human pregnancy, chorioamnionitis (CAM) frequently precedes genital tract and placental inflammation. It is a primary cause of maternal morbidity and a major antecedent of preterm premature rupture of the membranes (PPROM) and preterm delivery (PTD).¹ The latter complicates about 13% of live births in the United States and is the leading cause of perinatal morbidity and mortality.^2,3 During CAM, microbial species usually first ascend from the vagina and cervix to the uterus where they induce deciduitis. Despite the presence of intact membranes, microorganisms can ultimately invade the chorion, amnion, amniotic fluid, and fetus. Although positive microbial cultures are found in the amniotic fluid in 23% of women with PPROM,^4,5 19% displayed no signs of overt amniotic fluid infection.⁵ However, these samples contained elevated levels of neutrophil collagenase and elastase^5,6 suggesting that pathogens remained localized to the decidua or the inciting microorganisms escaped detection.⁵Recently, the large prospective Alabama Preterm Birth Study confirmed the strong association between CAM and the detection of bacterial infections. This study also observed a positive correlation between neutrophil infiltration of the fetal membranes, chorionic plate, and umbilical cord, which serve as markers of CAM, with positive intrauterine bacterial cultures and the occurrence of both the neonatal inflammatory response syndrome and necrotizing enterocolitis.⁷ However, in a significant subset of cases, a mononuclear infiltrate in the fetal membranes and decidua basalis proved to be a harbinger of neonatal intraventricular hemorrhage. Specifically, mononuclear cell infiltration was present in 10% of the placental free membranes and decidua basalis, and within this group there was a 24% increase in neonatal intraventricular hemorrhage. This study also found a positive correlation between PTD and significantly elevated umbilical cord blood levels of interleukin (IL)-6.⁷ The latter is a multifunctional cytokine that regulates hematopoiesis, the acute phase reaction, and both pro- and anti-inflammatory events.⁸ Our laboratory recently demonstrated that decidual cells (DCs), the predominant endometrial cell type throughout pregnancy⁹ are a major source of elevated maternal plasma IL-6 levels¹⁰ implicated in inducing systemic endothelial cell activation and vascular damage in preeclampsia.¹¹In the current study we hypothesized that DCs could also contribute to the well documented CAM-related increase in IL-6 levels in maternal plasma¹² as well as cervical and amniotic fluid IL-6 levels¹³ that reliably predict PPROM and PTD¹⁴ while acting as an autocrine/paracrine modulator of the local immune cell population. To shed light on these questions, immunohistochemistry was used to localize IL-6 at the maternal-placental interface in DCs of placental sections from patients with CAM and gestational age-matched control placentas. The effects of IL-1β, a classic proinflammatory cytokine present at elevated levels in the amniotic fluid of women with CAM,¹⁵ were evaluated on IL-6 mRNA and protein expression in cultured human term DCs. In these experiments, IL-1β was added with either estradiol (E₂) as the control incubation or with E₂ plus medroxyprogesterone acetate (MPA) to mimic the steroid milieu of pregnancy. To eliminate the confounding effects of resident immune cells, experimental incubations were performed with DCs that were passaged until fluorescence-activated cell sorter analysis indicated that they were essentially leukocyte-free. To elucidate a potential mechanism regulating IL-1β-enhanced IL-6 expression in human decidual cells, experimental incubations included specific inhibitors of the intracellular signal transduction pathways for p38 mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and nuclear factor (NF)-κB activation, which are all known to mediate IL-1β-enhanced IL-6 expression.^16,17 A functional in vitro assay determined whether elevated IL-6 levels in the conditioned medium of IL-1β-treated term DCs could promote differentiation of monocytes away from dendritic cells and toward macrophages.     

Effect of Cholesterol Depletion on Interleukin-8 Production in Human Respiratory Epithelial Cells

Purpose

The lipid entities of cell membranes are components of the immune system and important mediators of inflammation. Despite increasing interest in the function of epithelial cells in inflammation, the role of cholesterol in this process has not been described. Here, we investigated the effect of cholesterol depletion on the inflammatory process in airway epithelial cells via the expression of interleukin (IL)-8 as a marker of inflammation.

Methods

A 549 cells were treated with 0.5% methyl-β-cyclodextrin as a selective cholesterol extractor. The IL-8 level was assessed by enzyme-linked immunosorbent assay and reassessed after cholesterol repletion. Mitogen-activated protein kinase (MAPK) inhibitors were used to determine the upstream signaling pathway for IL-8 production in cholesterol-depleted cells.

Results

We found a relationship between the amount of cholesterol in A 549 cells and inflammation of the airway. IL-8 production was increased in cholesterol-depleted A 549 cells and restored by cholesterol repletion. IL-8 production was decreased by pretreatment with the extracellular signal-regulated kinase (ERK) inhibitor U0126 but not with JNK inhibitor II or the p38 MAPK inhibitor SB202190.

Conclusions

Our findings suggest that inflammatory responses are increased in cholesterol-depleted epithelial cells via the MAPK signaling system, predominantly by the ERK pathway. We conclude that the lipid components of airwayepithelial cells may play a role in the inflammatory process.     

Negative Regulation of Interleukin-1 in Immune Reactive Cells

Interleukin-1 (IL-1) is an immunological regulator with a multitude of effects. Recently, IL-1 inhibitors from urine, monocytes, or monocytic cell lines have been described, we previously demonstrated an IL-1 inhibitor from human monocytes under immune complex or immunoglobulin stimulation. The present studies were initiated to determine the production of IL-1 inhibitor from human polymorphonuclear cells (PMN), B and T lymphocytes in response to certain stimuli using a murine thymocyte system responsive to IL-1. My results indicated that the inhibitor is constitutively present in PMN because unstimulated PMN supernatants also show inhibitory activity. B and T lymphocytes can not produce IL-1 inhibitor under zymosan, immunoglobulin, or immune complex stimulation. The presence of this PMN inhibitor may also be important in the negative regulation of IL-1.     

Interleukin-10 Directly Inhibits the Interleukin-6 Production in T-Cells

IL-6 is a potent regulator of T-cell activation, proliferation and differentiation. Since IL-10 inhibits cytokine production by T cells, the effect of IL-10 on IL-6 production by T cells was investigated. IL-6 production by purified monocytes or T cells was detected from cell-free culture supernatants by ELISA after stimulation of the cells with LPS or an anti-CD3 monoclonal antibody for 3 days. Although the main source of IL-6 are LPS activated monocytes (29.6 × lOng/ml), T cells secreted sufficiently high levels of IL-6 (790 × 200pg/ml) to stimulate the high affinity IL-6 receptor. IL-10 decreased anti-CD3 induced IL-6 mRNA expression by up to 80%. In addition, IL-10 significantly inhibited IL-6 release from T-cells. Highly purified, anti-CD3 activated T-cells secreted 600 × 150pg/ml IL-6 compared to 21 × 2pg/ml IL-6 following addition of IL-10 (10ng/ml; P <0.001). FACS analysis revealed a monocyte contamination of the T-cell preparations of less than 0.5%. In addition, no IL-1 production was detectable. Thus, in our experiments the effect of TL-10 on IL-6 production was independent of the presence of monocytes. Finally, inhibition of IL-6 production was not reversed by IL-2 (100U/ml). In conclusion, IL-10 suppressed the synthesis of IL-6 by T-cells via a monocyte-and IL-2-independeni mechanism. These results may help to understand the complex regulation of T-cell mediated cytokine production by IL-10.     

Interleukin-1 Production by a Cloned Line of Human Monocyte-Like Cells (CM-SM)

Interleukin-1 (IL-1) production by the human monocyte-like cloned cell line CM-SM has been investigated as a function of the state of cell differentiation. CM-SM cells were induced to differentiate along the monocyte-macrophage lineage by bacterial lipopolysaccharides (LPS) or by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Cell differentiation was studied by various morphological, functional, cytochemical, and immunological variables, whereas IL-1 activity in the supernatants was measured by the lectin-primed thymocyte proliferation assay. Unstimulated CM-SM cells constitutively produced small amounts of IL-1, and most of the cells appeared relatively undifferentiated. LPS induced cell differentiation, but the effect was reversible, and the cells, in general, did not acquire a capacity for phagocytosis. IL-1 levels were increased about 10-fold over the controls. TPA induced further cell differentiation to macrophage-like cells capable of phagocytosis. IL-1 activity could not be measured directly in the supernatants owing to the synergistic effect of TPA in the assay system. Unequivocal removal of the phorbol was not achieved, but the data indicated that the 'real' levels of IL-1 in the TPA-induced cultures were not significantly higher than those from LPS-induced cultures.     

Regulation of Interleukin-2 Induced Soluble Fas Ligand Release from Human Peripheral Blood Mononuclear Cells

Adjuvant interleukin (IL)-2 immunotherapy has been used in the treatment of different malignant dieseases. However, clinical results have been rather disappointing. Therefore, further investigations on IL-2-induced mediators of cytotoxicity seem to be necessary in order to possibly create cytokine cocktails which could enhance the IL-2-induced cytotoxicity. We therefore investigated the regulation of IL-2-induced release of soluble Fas Ligand (sFasL), since this factor is known to possess anti-tumor activities. In CD3-stimulated peripheral blood mononuclear cells IL-2 induced sFasL in a dose-dependent fashion. Maximum sFasL concentrations were obtained after stimulation of MNC for 120 hrs. Inhibition of endogenous IL-12 production significantly reduced IL-2-mediated sFasL release by about 25%. In contrast, addition of IL-12 enhanced the IL-2-induced sFasL about 1,5-fold. IL-10 and IL-4 reduced the IL-2-stimulated sFasL by about 30%. Interestingly, these suppressive effects could be antagonized by the addition of IL-12. Not only exogenous IL-10 but also endogenously produced IL-10 decreased the sFasL release to that extent which had been stimulated by IL-12. Since IL-12 and IL-10 only marginally influenced the IL-2-mediated cell proliferation as well as the IL-2-induced cell death, the IL-12- and IL-10-controlled sFasL release seems to be based on an enhanced production per cell. However, the increase in cell numbers as well as the decrease of viability during cell culture might additionally contribute to the IL-2-induced increase of sFasL release. This secondary effect might explain why IL-2-mediated sFasL production is only partially controlled by regulatory cytokines such as IL-4, IL-10 or IL-12. In conclusion, addition of IL-12 might increase the efficacy of IL-2 immunotherapy by inhibition of the IL-10-mediated negative feed-back loop on IL-2-mediated sFasL release.     

Platelet-Activating Factor Stimulates Interleukin-6 Production by Human Endothelial Cells and Synergizes with Tumor Necrosis Factor for Enhanced Production of Granulocyte-Macrophage Colony Stimulating Factor

The interaction between human endothelial cells (EC) and leukocytes during inflammation is in part mediated through the release of soluble factors. Since platelet-activating factor (PAF) is a potent mediator of inflammatory responses, we investigated the potential of PAF to modulate IL-6 and GM-CSF production by EC. Exposure of these cells to PAF resulted in a concentration-dependent increase in IL-6 production, with a maximum at 10^–10 M PAF. Sequential incubation of EC with PAF and TNF resulted in a synergistic increase of IL-6 production. This effect was specific for PAF since it was prevented by preincubation with the PAF receptor antagonist, WEB 2086. Northern blot analysis revealed enhanced IL-6 mRNA expression in PAF-treated EC. However, the synergy observed in protein synthesis between PAF and TNF was not reflected in IL-6 mRNA accumulation, suggesting a post-translational modulation. Pretreatment of EC with the protein synthesis inhibitor cycloheximide before their exposure to PAF resulted, after washout of the cycloheximide, in a markedly augmented production of IL-6, suggesting a synergy between augmented IL-6 mRNA accumulation by PAF and IL-6 mRNA superinduction by cycloheximide. GM-CSF production by EC was also stimulated by the combined effects of PAF and TNF, but PAF alone did not affect GM-CSF production. Taken together, our data suggest that PAF can stimulate EC to synthesize cytokines, including IL-6 and GM-CSF, which may contribute to local and, possibly, systemic responses during inflammation.     

Activated Human Valvular Interstitial Cells Sustain Interleukin-17 Production To Recruit Neutrophils in Infective Endocarditis

The mechanisms that underlie valvular inflammation in streptococcus-induced infective endocarditis (IE) remain unclear. We previously demonstrated that streptococcal glucosyltransferases (GTFs) can activate human heart valvular interstitial cells (VIC) to secrete interleukin-6 (IL-6), a cytokine involved in T helper 17 (Th17) cell differentiation. Here, we tested the hypothesis that activated VIC can enhance neutrophil infiltration through sustained IL-17 production, leading to valvular damage. To monitor cytokine and chemokine production, leukocyte recruitment, and the induction or expansion of CD4⁺ CD45RA⁻ CD25⁻ CCR6⁺ Th17 cells, primary human VIC were cultured in vitro and activated by GTFs. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA), and neutrophils and Th17 cells were detected by immunohistochemistry in infected valves from patients with IE. The expression of IL-21, IL-23, IL-17, and retinoic acid receptor-related orphan receptor C (Rorc) was upregulated in GTF-activated VIC, which may enhance the proliferation of memory Th17 cells in an IL-6-dependent manner. Many chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), were upregulated in GTF-activated VIC, which might recruit neutrophils and CD4⁺ T cells. Moreover, CXCL1 production in VIC was induced in a dose-dependent manner by IL-17 to enhance neutrophil chemotaxis. CXCL1-expressing VIC and infiltrating neutrophils could be detected in infected valves, and serum concentrations of IL-17, IL-21, and IL-23 were increased in patients with IE compared to healthy donors. Furthermore, elevated serum IL-21 levels have been significantly associated with severe valvular damage, including rupture of chordae tendineae, in IE patients. Our findings suggest that VIC are activated by bacterial modulins to recruit neutrophils and that such activities might be further enhanced by the production of Th17-associated cytokines. Together, these factors can amplify the release of neutrophilic contents in situ, which might lead to severe valvular damage.     

Fibrinogen and Its Oxidized Form Induce Interleukin-2 Production in Cultured Endothelial Cells of Human Vessels

Oxidized fibrinogen was more potent than native fibrinogen in inducing interleukin-8 production in primary culture of human endothelial cells. The optimal concentration of oxidized fibrinogen was 3 mg/ml. The optimal time of UV irradiation was 17 min. Secretion of interleukin-8 was maximum during culturing of endothelial cells in a serum-free medium.     

Interleukin-6 and Interleukin-6 Receptor are Expressed by Cultured Glomerular Epithelial Cells

Interleukin-6 (IL-6) has been extensively studied in mesangial cells but little is known about the expression of this cytokine and its receptor in glomerular epithelial cells (GEC). IL-6 was detected in the culture supernatants of human GEC and its production was enhanced in time and dose dependent manner by lipopolysaccharide (LPS), interleukin-1β (IL-Iβ) and tumour necrosis alpha (TNF-α). Quiescent, serum-starved GEC did not express clearly IL-6 mRNA. Stimulation of cells with LPS, TNF-α or IL-1β resulted in an increase of detectable IL-6 mRNA. Interestingly, it was found that IL-6 induced its own mRNA attesting that this cytokine was secreted in autocrine fashion by GEC. GEC expressed IL-6 receptor (IL-6R) as demonstrated directly by the existence of IL-6R mRNA detected by northern blotting. Stimulation of GEC by pro-inflammatory mediators such as LPS increased the expression of IL-6R mRNA. The soluble form of IL-6 receptor (sIL-6R) was not detectable in the culture supernatants harvested from untreated or cytokine-treated cells. We investigated further, whether IL-6 may influence growth of cultured GEC. Incubation of GEC with recombinant (r) IL-6 resulted in a dose dependent increase in ³H thymidine incorporation indicating that IL-6 acts as an autocrine growth factor for GEC. We conclude that GEC are a potent source of IL-6, the local excessive expression of IL-6 and its receptor may play a substantive role in the regulation of processes which appear critical to the initiation of progressive glomerular disease such as cell proliferation.     

Carvedilol Modulates In-Vitro Granulocyte-Macrophage Colony-Stimulating Factor-Induced Interleukin-10 Production in U937 Cells and Human Monocytes

Both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-10 (IL-10) are important mediators regulating inflammatory responses. Inflammatory processes have an important role in atherogenesis. In this paper, the effects of carvedilol on GM-CSF-induced IL-10 production were examined on human monocytic cell line, U937, and purified human monocytes. First, we showed that one-time carvedilol pretreatment at concentrations 0.3-10 μM dose-dependently inhibited GM-CSF-induced IL-10 production in U937 cells. In addition, we found carvedilol to be non-cytotoxic at concentrations equal to or less than 10 μM. However, at concentrations higher than 10 μM, carvedilol induced programmed cell death in U937 cells. The inhibition of GM-CSF-induced IL-10 production by carvedilol was also observed at the expression of mRNA. Furthermore, the inhibition of IL-10 production was demonstrated in GM-CSF-activated purified human peripheral blood monocytes. Finally, long-term carvedilol pretreatment of U937 cells up to 2 months at concentrations of 1.0 μM mildly enhanced the IL-10 production. Our observations that carvedilol modulated GM-CSF-induced IL-10 production may have some implication in understanding the broad-spectrum effects of carvedilol in regulating inflammatory reactions.     

人胎儿胃肥大细胞的研究

观察了 40例不同胎龄胎儿胃底部两型肥大细胞发育、数量及分布和胃底部发育的关系 ,并探讨了甲醛固定对 CTMC和 MMC染色效应的影响。发现人胎儿胃 CTMC出现于受精后 13～ 16周的粘膜下层等处 ,主要分布在胃粘膜固有层近粘膜肌处 ,数量随粘膜层胃底腺及粘膜肌等结构的发育而增加。两型肥大细胞对甲醛固定的反应无明显差异。本文就肥大细胞在胃底部发育过程中的意义进行了讨论     

Catecholamine Storing Cells in Human Fetal Superior Cervical Ganglion

The distribution and structure of small, intensively fluorescent, granule-containing cells within the human feta! ganglion cenicale superius was studied. The ganglia contained numerous small collections of these cells evenly scattered over the whole region of the organ. The granule-containing cells were as a rule located on the capillaries and showed regularly tight contacts with the basement membrane. The mean diameter of the catecholamine storing granules was 2700 A. The differentiation and role of the granule-containing cells within sympathetic nervous system was discussed.     

Constitutive Secretion of Interleukin-6 by Human Decidual Stromal Cells in Culture. Regulatory Effect of Progesterone

PROBLEM : Although several studies have demonstrated that decidual stromal cells (DSC) can secrete cytokines in culture, none of these studies documented the purity of the cultures. Since other cells of the decidua, such as macrophages and epithelial cells, also produce cytokines, it is important to ensure purity of the culture so that cytokine production can be ascribed with confidence to DSC. METHOD : DSC from early human pregnancies were highly purified and maintained in culture. Basal secretion by these cells of IL-6, together with other cytokines considered critical for pregnancy (IL-1β, TNFα and IFNγ), was measured with immunological techniques. RESULTS : We found that DSC in culture produce insignificant quantities of IL-1β, TNFá and IFNΓ, but appreciable amounts of IL-6. The production of this later cytokine was, however, inhibited by the effect of progesterone. CONCLUSIONS : Basal production of IL-6 by DSC may be involved in physiological functions at the maternal-fetal interface. Nevertheless, the secretion of this cytokine is regulated by progesterone, probably to prevent excessive production of this cytokine from triggering an inflammatory response that might compromise pregnancy.     

Effect of Lipopolysaccharide and Inflammatory Cytokines on Interleukin-6 Production by Healthy Human Gingival Fibroblasts

Cytokines are hormone-like proteins which mediate and regulate inflammatory and immune responses. The purpose of this study was to investigate the effect of lipopolysaccharide (LPS) and inflammatory cytokines on regulation of interleukin-6 (IL-6) production by human gingival fibroblasts (HGF). The HGF cell lines used in this study, H-CL and F-CL, were established by the explant technique from healthy gingival tissue. Cultured cells were grown to confluency and incubated with various concentrations of LPS from Escherichia coli or Porphyromonas gingivalis or with the recombinant human cytokine tumor necrosis factor alpha (TNF-α), IL-1α, or IL-1β. Culture supernatants were collected at various times and assessed for IL-6 production by enzyme-linked immunosorbent assay. Total RNA was isolated from the harvested cells and used to assess levels of IL-6 mRNA by the RNase protection assay. Both LPS preparations induced IL-6 production (1 to 4 ng of IL-6 per ml) by both HGF cell lines. Although TNF-α stimulated IL-6 production by HGF, >10-fold-larger amounts were induced with IL-1α and IL-1β. Furthermore, the addition of both IL-1α and TNF-α to cultured cells resulted in approximately 600- to 800-fold-higher levels of IL-6 than seen in control cultures, suggesting that these cytokines synergistically induced IL-6 production by HGF. IL-6 message in cultured cells was upregulated 20-fold by TNF-α, 1,000-fold by IL-1α and IL-1β, and 1,400-fold by IL-1α plus TNF-α. IL-1α and TNF-α alone upregulate IL-6 production in a dose- and time-dependent fashion. The addition of IL-1α and TNF-α to cultured HGF cells resulted in a synergistic induction of IL-6 after 8 h of incubation and when greater than 10 pg of this combination per ml was used. Our studies show that inflammatory cytokines are hundreds of times more potent than LPS in stimulating IL-6 production by HGF.     

人胚胎小肠CgA-IR细胞的形态学研究

目的　探讨人胚胎小肠嗜铬素A免疫反应 (CgA IR)细胞的形态学发生、发育规律。方法　应用免疫组织化学方法 ,对 4 0例 6～ 38周人胚胎小肠CgA IR细胞进行研究。结果　人胚胎小肠CgA IR细胞于胚胎第 7周出现 ,主要分布在肠腺和绒毛上部 ,细胞大小不一 ,形态多样。人胚胎小肠CgA IR细胞在十二指肠最多、空肠次之、回肠最少 ;各肠段CgA IR细胞数随胎龄而增多 ,6月后则逐渐减少。 结论　CgA IR细胞于胚胎第 7周出现 ,其数量因肠段、部位和胎龄而不同     

Cytomegalovirus Infection Induces Production of Human Interleukin-10 in Macrophages

Earlier findings have suggested that the balance between interleukin-10 and tumor necrosis factor levels in serum may influence the outcome of cytomegalovirus infection in renal transplant recipients. Therefore, the aim of the present study was to investigate whether human cytomegalovirus induces interleukin-10 production in macrophages. Experiments using human cytomegalovirus (strain 2006), ultraviolet-inactivated cytomegalovirus, and mock-infected differentiated THP-1 cells with or without ganciclovir or monoclonal anti-tumor necrosis factor antibodies were performed. Cytomegalovirus-infected cells produced significantly higher levels of human interleukin-10 mRNA and interleukin-10 than ultraviolet-inactivated cytomegalovirus or mock-infected cells. The addition of ganciclovir had little effect on interleukin-10 production. Anti-tumor necrosis factor antibodies appeared to reduce the interleukin-10 levels. In conclusion, human cytomegalovirus infection of macrophages induces production of human interleukin-10. This requires viral entry, but not full viral replication.