白细胞介素-8在妊娠早期小鼠子宫内膜的表达及对胚泡着床的影响

目的：研究白细胞介素-8（IL-8）在妊娠早期小鼠子宫内膜的表达及其对小鼠胚泡着床的影响。方法：用免疫组化法及图像分析技术对IL-8在妊娠1～6d小鼠子宫内膜的表达进行定位和测定;子宫角注入IL-8抗体,探讨IL-8对胚泡着床的影响。结果：在子宫内膜腔上皮,IL-8主要定位于细胞的游离面,妊娠1d阳性反应最弱,4d表达最强,5d有所下降,6d又开始增强;在子宫内膜腺上皮,妊娠4d表达最弱,5d和6d最强;在子宫内膜的基质细胞,随妊娠天数增加,IL-8的表达逐渐增强。IL-8Ab明显抑制小鼠胚泡着床。结论：IL-8在妊娠早期小鼠子宫内膜持续表达,并参与胚泡的着床调控过程。     

Altered expression of pro-inflammatory and developmental genes in the fetal brain in a mouse model of maternal infection

Human studies of unexplained cerebral palsy (CP) suggest an association with maternal infection. We used an established model of maternal infection, lipopolysaccharide (LPS) administration, to investigate the molecular changes in the fetal brain that may link maternal infection and CP. We compared gene expression in brains from mouse pups exposed to LPS in utero to those from saline-treated controls. Dams were injected with 50 microg LPS or saline on E18 with surgical delivery from 0.5 to 6h later. Differential gene expression was analyzed in the whole mouse brain using RT-PCR. When compared to control mice, pups exposed to LPS showed increased expression of pro-inflammatory genes monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta), as well as VEGF, a regulator of vascular development and permeability, the anti-apoptotic protein Y-box-binding protein-1 (YB-1), and the neuronal differentiation factor necdin. LPS-exposed mice also showed downregulation of semaphorin 5b and groucho, involved in axon guidance and neurogenesis, respectively, providing evidence that LPS may disrupt normal developmental pathways. These data suggest possible mechanisms for adverse neurological outcomes following maternal infection involving elevated cytokine levels and altered expression of developmental genes in the fetal brain.     

Mitogenic effect of platelet-derived growth factor in human glomerular mesangial cells: modulation and/or suppression by inflammatory cytokines.

Glomerular mesangial cell proliferation constitutes a frequent pathological alteration in glomerulonephritis. In addition to platelet-derived growth factor (PDGF) inflammatory cytokines such as IL-1, IL-6 or tumour necrosis factor-alpha (TNF-alpha) have been proposed to have mitogenic activity for mesangial cells. A model was therefore established in which human mesangial cells (HMC) could be reversibly growth-arrested for prolonged times in serum-free medium without suffering irreversible functional or morphological changes. In this model 24 h stimulation with rhPDGF-BB induced an increase of the 3H-thymidine incorporation of 1190 +/- 280 (50 ng/ml) % +/- s.e.m. of medium control. Less growth induction was noted after stimulation with 50 ng/ml rhPDGF-AB (925 +/- 126%) or rhPDGF-AA (575 +/- 24%). Northern analysis confirmed the presence of both alpha- and beta-PDGF receptor subunit mRNA in growth-arrested HMCs. rhIL-1 alpha, rhIL-1 beta, rhTNF-alpha or rhIL-6 at various doses and times, despite increasing cellular PGE2-release, did not induce significant proliferation in HMCs. Inhibition of PGE2-release did not change the lack of mitogenicity of IL-1, TNF-alpha or IL-6. IL-6 did not alter the mitogenic response of the cells towards PDGF. In contrast, both IL-1 alpha and IL-1 beta (5 ng/ml) induced a delay but not augmentation of the PDGF growth response. This delay could be reversed by the concomitant addition of recombinant IL-6 or of anti-IL-1 antibody but not by inhibition of prostaglandin synthesis. High doses of TNF-alpha suppressed PDGF-induced proliferation. These data suggest that in growth-arrested HMCs inflammatory cytokines have a growth-modulating or -suppressive rather than (co-)mitogenic effect while PDGF-BB and -AB and to a lesser degree PDGF-AA are potent mitogens. The findings support the notion that the control of HMC proliferation in pathological situations depends on a complex network of interacting stimuli.     

Progressive rise in the expression of interleukin-6 in human endometrium during menstrual cycle is initiated during the implantation window

In order to be prepared for implantation, human endometriumundergoes a predictable series of proliferative and secretorychanges. Cytokines play an important role in regulation of thesechanges. Therefore, in this study, we immunolocalized the cytokine,interleukin-6 (IL-6), its receptor and the signal transducergp130 in human endometrium throughout the menstrual cycle. Duringthe entire menstrual cycle, the IL-6 receptor and gp130 werefound primarily in the endometrial glands and to a lesser extentin the stroma. The immunoreactivity of these proteins did notchange in endometrial cells during the entire menstrual cyclewith an exception of reduced immunoreactivity of gp130 in endometrialglands during menstrual phase. Immunostaining showed that immunoreactiveIL-6 was weakly expressed in human endometrium during the proliferativephase. Strong immunoreactivity for IL-6 appeared in endometriumduring the putative 'implantation window'. Expression was byfar most pronounced both in the glandular and surface epithelialcells. The amount of immunoreactive IL-6 in the epithelium progressivelyincreased during the secretory/menstrual phases. During thelate secretory phase, only stromal cells in the upper functionalisexhibited immunoreactivity for IL-6. Western blot analysis corroboratedthe immunohistochemical data. Human endometrial IL-6 consistedof a protein with an apparent mobility of 26 kDa. The immunoreactiveband of IL-6 was weak in the proliferative phase. The expressionof this protein increased progressively during the secretory/menstrualphases. The findings show a cell-specific pattern of distributionfor immunoreactive IL-6 in human endometrium. The menstrualcycle-dependent expression of IL-6 suggests that this cytokinemay play a role in changes in endometrium that prepare thistissue for implantation and menstrual shedding.     

Acute release of cytokines is proportional to tissue injury induced by surgical trauma and shock in rats

Cytokines are important mediators of the inflammatory reaction and microvascular injury after trauma and tissue ischemia. The plasma activity of a cytokine reflects the net effect of positive and negative signals. We examined the sequential serum activity of IL-1, IL-2, IL-6, and TNF in a severe model of splanchnic artery occlusion (SAO) shock induced in rats by total occlusion of the superior mesenteric and the celiac arteries for 40 min. A control group with negligible surgical intervention and two sham-shock groups, one with minor operation and another with major surgery employed in SAO rats, both without vascular occlusion, were also studied. No IL-1 activity was detected throughout the 190-min experimental protocol in any of the groups. Low activity of IL-2 was measured only in SAO rats (1 U/ml at the peak). We found graded increases in serum TNF and IL-6 activities which were proportional to the surgical trauma and were highest in SAO rats (IL-6 up to 30 U/ml,P<0.01 from both sham groups; TNF, 2500 pg/ml 30 min after reperfusion,P<0.01 from both sham groups). These data further support the role played by cytokines in the early mediation of surgical trauma and shock.This study was carried out in adherence with the NIH guidelines for the use of experimental animals.     

The mycotoxins citrinin and gliotoxin differentially affect production of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6, and the anti-inflammatory cytokine interleukin-10

BACKGROUND: Microbial growth is considered one of the major causes of indoor air problems. Moulds have been associated with asthma, allergy and a wide range of diffuse indoor air-related symptoms. However, mechanisms of the adverse health effects are not well understood. OBJECTIVE: We hypothesized that the mycotoxins citrinin and gliotoxin could cause an imbalance between the secretion of the pro-inflammatory cytokines TNF-alpha and IL-6 and the anti-inflammatory cytokine IL-10. METHODS: We investigated the influence of citrinin and gliotoxin on the human monocytic cell line Mono-Mac-6 (MM6) with and without lipopolysaccharide -stimulation. The levels of IL-10, IL-6 and TNF-alpha were analysed in cell culture supernatants by ELISA. Cell viability and cell apoptosis were measured by flow cytometry. RESULTS: The strongest inhibition of cytokine secretion was found for IL-10. IL-6 levels were found to decrease in a dose-dependent manner along with reduced cell viability. TNF-alpha levels increased with low gliotoxin exposure (less than 100 ng/mL), but decreased significantly at 375 ng/mL and higher along with increased cell apoptosis and reduced cell viability. TNF-alpha levels were not reduced by citrinin exposure. CONCLUSION: We observed a cytokine imbalance with a more pronounced reduction of IL-10 concentrations compared with those of TNF-alpha and IL-6. We suggest that low exposure doses of citrinin and gliotoxin (corresponding to less than 100 ng/mL gliotoxin and less than 10 mug/mL citrinin) may inhibit IL-10 and lead to increased risk of an inflammatory response with relative overproduction of TNF-alpha and IL-6. The findings and their clinical implications must be verified by human studies. However, we speculate that the observed biological effects may be of importance as they may partly explain the occurrence of diffuse general indoor air-related symptoms as well as the worsening of asthmatic inflammatory reactions experienced in mouldy environments.     

孕酮对自然流产小鼠白细胞介素6表达的影响

目的:探讨孕酮对自然流产小鼠母胎界面白细胞介素6(IL-6)的调节作用.方法:建立经典的自然流产动物模型(CBA/J×DBA/2),用免疫组织化学显色和RT-PCR检测自然流产小鼠蜕膜及绒毛组织中IL-6蛋白和mRNA的表达情况.结果:孕酮组血清孕酮水平明显高于模型组,IL-6水平高于模型组.孕酮组血清孕酮、IL-6水平与正常组比较均无差异.免疫组织化学显色和RT-PCR结果显示,在绒毛组织中,孕酮组IL-6蛋白相对含量显著高于模型组,IL-6 mRNA相对含量高于模型组,两者与正常组比较均无差异;在蜕膜组织中,孕酮组IL-6蛋白的相对含量低于模型组,IL-6 mRNA相对含量高于模型组,与正常组比较均无差异.结论:孕酮通过上调IL-6的表达来减少自然流产的发生和发展,而且孕酮调节Th1/Th2细胞因子平衡的作用发生在母胎界面.     

The IL1A genotype is associated with nasal polyposis in asthmatic adults

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease often found coexisting with asthma. As this disorder tends to cluster in families, a genetic predisposition has been suggested. Interleukin-1 (IL-1) has been proposed to play a role in the pathogenesis of NP. METHODS: We analysed the single G-to-T base exchange polymorphism in exon 5 at +4845 of the gene encoding IL-1alpha (IL1A) and the C-to-T base exchange polymorphism at -511 of the gene encoding IL-1beta (IL1B) in a population-based sample of adult asthma patients (n = 245). The data were assessed for correlation with data on history of NP and other phenotype-related characteristics. RESULTS: The prevalence of NP in our study group was 14.3%. The distribution of the IL1A genotype differed significantly between asthmatics with and without NP (P = 0.005). The risk of NP was markedly increased in allele G homozygous subjects (OR = 2.73; 95%CI = 1.40-5.32). In the case of IL1B we found no significant associations. Asthmatics with NP had more symptoms than others, but lung function and blood eosinophil counts were similar. CONCLUSIONS: Our study demonstrates an association of IL1A with NP inasthmatic patients and addresses the role of IL-1alpha as an inflammatory modulator in the pathogenesis of this disease.     

Adenoviral interleukin-12 gene transduction into human bronchial epithelial cells: up-regulation of pro-inflammatory cytokines and its prevention by corticosteroids

BACKGROUND: One of the potential effects of IL-12 is to restore Th1/Th2 balance. Therefore, we investigated the possibility of developing a system for local delivery of IL-12 into the airways by examining protein expression in a human bronchial epithelial cell line (BEAS-2B) after adenoviral IL-12 gene transduction. The effects of dexamethasone on the gene-modified cells were also examined. MEHODS: Adenoviral vectors AxCAegfp and Ax1CIhp40ip35 were used to transduce enhanced green fluorescence protein and IL-12 genes, respectively, into BEAS-2B cells. Wild-type and IL-12 gene-transduced BEAS-2B cells were then incubated with or without dexamethasone, and concentrations of IL-12, IFN-gamma, IL-6, IL-8, granulocyte macrophage-colony stimulating factor and chemokines (TARC and RANTES) in the supernatant were measured by ELISA. IL-12 receptor expression was analysed by flow cytometry and RT-PCR. RESULTS: The efficiency of transgene expression in BEAS-2B cells at a multiplicity of infection of 30 was approximately 80%. Gene-modified BEAS-2B cells produced biologically active IL-12, regardless of dexamethasone treatment. While IL-12 gene transduction led to increased production of IL-6 and IL-8 by BEAS-2B cells, expressions of these proteins were suppressed by dexamethasone. Addition of exogenous IL-12 failed to augment BEAS-2B cell IL-6 and IL-8 production, and IL-12 receptor expression by BEAS-2B cells was not detected. CONCLUSIONS: Our findings suggest that adenoviral IL-12 gene transduction may be effective in inducing IL-12 expression in the airways, and could be a potential approach in the management of bronchial asthma.     

Co-expression of TNF alpha and IL-1 beta in human acute pulmonary fibrotic diseases: an immunohistochemical analysis

To clarify the involvement of TNF alpha and IL-1 beta in the initiation of fibrotic lung diseases, their localization was examined by immunohistochemistry. Fibrotic lung diseases observed were classified into acute and old pulmonary fibrotic changes. The acute fibrotic changes included adult respiratory distress syndrome, acute interstitial pneumonia and idiopathic pulmonary fibrosis with acute exacerbation. Acute pulmonary fibrotic changes histopathologically corresponded to a mixture of the exudative and proliferative phases of diffuse alveolar damage. Both TNF alpha and IL-1 beta were positive in the alveolar macrophages and proliferating type II pneumocytes in acute fibrotic changes. In contrast, positive cells for TNF alpha and IL-1 beta were sparse in the areas of old fibrotic change and in the normal tissue. These findings suggest that TNF alpha and IL-1 beta play an important role in the initiation of pulmonary fibrotic responses and in the architectural remodeling, irrespective of the etiology of fibrotic lung diseases.     

CPAF,HSP60 and MOMP antigens elicit pro-inflammatory cytokines production in the peripheral blood mononuclear cells from genital Chlamydia trachomatis-infected patients

Background

Persistent inflammation caused by Chlamydia trachomatis in the female genital compartment represents one of the major causes of pelvic inflammatory disease (PID), ectopic pregnancy and infertility in females. Here, we examined the pro-inflammatory cytokine response following stimulation with three different types of C. trachomatis antigens, viz. chlamydial protease-like factor (CPAF), heat shock protein 60 (HSP60) and major outer membrane protein (MOMP).

Immune regulation at the interface during early steps of murine implantation: involvement of two new cytokines of the IL-12 family (IL-23 and IL-27) and of TWEAK

PROBLEM: An important subset of implantation defects/early abortion seems to be linked with a deregulation of the interleukin (IL)-12/IL-15/IL-18 system as well as tumor necrosis factor (TNF)- and natural killer (NK)-controlled/mediated networks at the decidual placental interface, both in case of deficient or excess expression. The presence of TNF in high amounts in the pre/peri-implantation uterus and its pivotal role during pregnancy are difficult to reconcile with its abortive effects in ongoing pregnancy. We therefore searched for regulators of the IL-12/IL-18 family of cytokines as well as for antagonist(s) of TNF with potentially selective effects on implantation. METHOD OF STUDY: We first used Swiss mice to verify the presence in the murine reproductive tract of 'new members' of the IL-12 family of cytokines, IL-23 and IL-27, as well as of tumor necrosis factor-like WEAK inducer of apoptosis (TWEAK), described as acting with TNF as Yin and Yang of innate immunity in murine placenta/ decidua at days 0-12.5. We then compared expression by RT-PCR in the CBA x DBA/2, and CBA x BALB/c murine mating combinations. Finally, we performed in vivo neutralization experiments of TWEAK and IL-27. RESULTS: Immunohistochemistry (IHC) studies showed that IL-23, IL-27, and TWEAK were expressed at the interface. For RT-PCR, IL-23 expression peaked at day 9.5 in the non-aborting mating combination, a peak absent in the aborting one, and thus difficult to explain except by invoking a feed back on EB13 (Epstein-Barr virus-induced gene 3 cytokine). Most important, an immediate post-mating IL-27 hyper expression was seen in the CBA x DBA/2 mating compared to CBA x BALB/c one. The difference in expression resurged and was statistically very significant by days 6.5-9.5, compatible with an early activation of inflammation on day 0.5 which would then peak again in the 'resorption window' where takes place the early NK/mph activation described by Baines et al. A significant TWEAK expression was present in both strains from days 0.5 to 4.5 peaking in both cases in the first days when it is known that intra uterine TNF also reaches high levels as a component of post-mating inflammation. However, it was lower from day 1.5 in the abortion-prone CBA x DBA/2 mating combination, and almost absent by days 6.5-9.5 when compared to the non-aborting CBA x BALB/c mating combination. In both mating combinations, neutralization of TWEAK-enhanced resorption rates, but surprisingly so did IL-27 neutralization. CONCLUSION: TWEAK is likely offering protection against the deleterious effects of TNF in implantation explaining embryo survival in a TNF-rich environment, and equal number of implants in both strains. However, there is a clear difference of protection in abortion-prone mating peaking in the abortion/resorption window but starting early, and therefore possible links with the prevention of abortion in CBA x DBA/2 matings by interfering with complement activation as recently described by Girardi et al. are discussed, as well as consequences for our current view of feto-maternal 'seed and soil' interplay. The apparently paradoxical effects of IL-27 neutralization are also discussed.     

Expression of oestrogen receptors alpha and beta during the period of uterine receptivity in rat: effect of ormeloxifene, a selective oestrogen receptor modulator

Aims: In the present study, we investigated expression, distribution and regulation of oestrogen receptors (ERs) α and β and their modulation by ormeloxifene (Orm) during the period of uterine receptivity in rat uterus in order to determine their role in endometrial sensitization. Methods: Uterine tissues of control and Orm‐treated (1.25 mg kg^?1, orally) rats were collected on days 3, 4, 5 morning and day 5 evening post‐coitum referring to non‐receptive, pre‐receptive and receptive phases respectively. mRNA and protein expression levels were determined by RT‐PCR and Western blot respectively. Immunohistochemical technique was used to localize the receptors. Results: RT‐PCR analysis revealed that ERα mRNA reached a peak level on day 5 morning whereas ERβ mRNA expression was found to be very low. In Orm‐treated rats, the ERα mRNA was suppressed at day 5. The protein expression of ERα increased after day 3 and that of ERβ remained very low throughout the pre‐implantation period; Orm caused a decrease in ERα on day 5 morning. In endometrium, ERα expression was regulated differentially in luminal epithelium, glandular epithelium and stroma. Orm caused a decrease in the percentage of ERα‐positive nuclei in all the three endometrial compartments on days 4 and 5, and the magnitude of reduction varied spatio‐temporally. In case of ERβ, immunostaining was not detectable in Orm‐treated and control groups. Conclusion: It appears that the complex uterine response to implantation is governed by differential cell‐specific ERα expression. The study suggested the inhibitory activity of Orm on ERα during the period of uterine receptivity.     

The strength of B cell immunity in female rhesus macaques is controlled by CD8+ T cells under the influence of ovarian steroid hormones

To understand more clearly how mucosal and systemic immunity is regulated by ovarian steroid hormones during the menstrual cycle, we evaluated the frequency of immunoglobulin- and antibody-secreting cells (ISC, AbSC) in genital tract and systemic lymphoid tissues of normal cycling female rhesus macaques. The frequency of ISC and AbSC was significantly higher in tissues collected from animals in the periovulatory period of the menstrual cycle than in tissues collected from animals at other stages of the cycle. The observed changes were not due to changes in the relative frequency of lymphocyte subsets and B cells in tissues, as these did not change during the menstrual cycle. In vitro, progesterone had a dose-dependent inhibitory effect, and oestrogen had a dose-dependent stimulatory effect on the frequency of ISC in peripheral blood mononuclear cell (PBMC) cultures. The in vitro effect of progesterone and oestrogen on ISC frequency could not be produced by incubating enriched B cells alone with hormone, but required the presence of CD8+ T cells. Following oestrogen stimulation, a CD8+ enriched cell population expressed high levels of IFN-gamma and IL-12. The changes in B cell Ig secretory activity that we document in the tissues of female rhesus macaques during the menstrual cycle is due apparently to the action of ovarian steroid hormones on CD8+ T cells. Thus, CD8+ T cells control B cell secretory activity in both mucosal and systemic immune compartments. Understanding, and eventually manipulating, the CD8+ regulatory cell-B cell interactions in females may produce novel therapeutic approaches for autoimmune diseases and new vaccine strategies to prevent sexually transmitted diseases.     

加味宣肺透解剂对流感病毒感染小鼠细胞因子的影响

目的：观察加味宣肺透解剂（JXT）对流感病毒感染小鼠细胞因子的影响。方法：复制流感病毒鼠肺适应株（FM1）小鼠肺炎模型，以加味宣肺透解剂灌胃治疗。ELISA法检测感染后第5天血清中IL-2、TNF-α、IL-6、IFN-γ的含量，肺组织切片HE染色。结果：加味宣肺透解剂明显升高血清中IL-2、IFN-γ水平，降低TNF-α、IL-6水平，减轻肺组织病变。结论：调节细胞因子的分泌，可能是加味宣肺透解剂减轻病毒感染小鼠肺组织损伤的机制之一。     

Maternal serum levels of pro-inflammatory cytokines in missed and threatened abortion

PROBLEM: A study of association between pro-inflammatory cytokines, and missed and threatened abortions with good outcome has been performed. METHOD OF STUDY: The presence of pro-inflammatory cytokines, namely interleukin (IL)-8 and IL-12 and the soluble interleukin-2 receptor (SIL-2R) was investigated in maternal serum of 12 patients with threatened abortion twice (at admission and discharge), 14 patients with missed abortion, 14 women with healthy first-trimester pregnancy, and 14 normal non-pregnant women, using specific enzyme-linked immunosorbent assays. RESULTS: SIL-2R and, in particular, IL-12 was detected with significantly higher levels in missed abortion group compared with all other groups. IL-8 was detected with no significant difference among all the groups studied. CONCLUSIONS: In spite of caution due to the small sizes of the subject samples, these results support a role of the immune system in the first trimester pregnancy and hypothesize that missed abortion may be associated with an enhanced Th1 reactivity, whereas threatened abortion with good outcome resembles the normal pregnancy with a non-enhanced Th1 reactivity.     

ICAM-1 and alpha3beta1 expression by bronchial epithelial cells and their in vitro modulation by inflammatory and anti-inflammatory mediators

BACKGROUND: Adhesion molecules are involved in inflammatory and repair processes of the bronchial epithelium. ICAM-1 is mainly involved in inflammatory reactions, whereas integrins, such as alpha3beta1, are mainly involved in repair processes. METHODS: Using bronchial biopsies from 10 asthmatics and eight controls, we first evaluated by immunohistochemistry expression of alpha3beta1 and ICAM-1 in intact and damaged epithelium. Then, using the human pulmonary epithelial cell line WI-26 VA, we studied, by flow-cytometry, the modulation of ICAM-1 and alpha3beta1 expression, and, by ELISA, the release of fibronectin by proinflammatory cytokines, such as IL-5, and anti-inflammatory cytokines, such as IL-4, TGF-beta, and EGF. RESULTS: alpha3beta1 expression was slightly higher in asthma than in controls, as well as in damaged epithelium than in undamaged epithelium. ICAM-1 expression was higher in asthma than in controls, and similarly distributed in intact or damaged epithelium. In vitro, alpha3beta1 was significantly increased by TGF-beta, EGF, and IL-4, and significantly decreased by IL-5. Fibronectin release was significantly increased by TGF-beta and IL-4, unchanged by EGF, and slightly but significantly decreased by IL-5. ICAM-1 expression was significantly decreased by TGF-beta and IL-4, unchanged by EGF, and significantly increased by IL-5. CONCLUSIONS: These differences in adhesion molecule expression and fibronectin release may be important in epithelial cell inflammation and repair.     

Downregulation of inflammatory mediators and pro-inflammatory cytokines by alkaloids of jeevaneeya rasayana in adjuvant-induced arthritis

Jeevaneeya rasayana is an ayurvedic polyherbal formulation, with antirheumatic potential. The present study investigates the therapeutic efficacy of isolated total alkaloid fraction of Jeevaneeya Rasayana (AJR) in treating rheumatoid arthritis in a rat model of Adjuvant-induced arthritis (AIA). Paw swelling, inflammatory mediators such as cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), level of prostaglandin E₂ (PGE₂), expression of cytokines and serum nitric oxide (NO) level were analyzed in experimental rats after an experimental period of 21 days. Arthritic induction significantly increased paw edema, and up regulated the inflammatory mediators and cytokines. Administration of AJR significantly reversed the paw edema, reduced the level of PGE₂, serum NO and decreased the COX-2 activity in the paw tissue. AJR treatment also downregulated mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and MMP-9 in paw tissue. HPTLC analysis revealed the presence of 5 different alkaloid compounds in AJR. These findings suggest that the AJR have the therapeutic potential against adjuvant-induced arthritis.     

Plasma cytokine levels in patients with obstructive sleep apnea syndrome: a preliminary study

The levels of some pro- and anti-inflammatory cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, and transforming growth factor (TGF)-beta], were measured by enzyme-linked immunosorbent assay (ELISA) method in the plasma of patients affected by obstructive sleep apnea syndrome (OSAS) at 22:00 hours before polysomnographic recording and immediately after the first obstructive apnea causing an SaO2 below 85%. Significantly higher levels of TNF-alpha were found in OSAS patients assessed before polysomnography compared with the control group (P < 0.01). A slight but significant increase in the plasma levels of IL-6 was also present (P < 0.05). Conversely, a significant decrease in the plasma levels of IL-10 was evident at baseline in OSAS patients (P < 0.04). No significant difference emerged between the mean values of IL-1alpha and TGF-beta between OSAS patients and controls. The present data support a prevailing activation of the Th1-type cytokine pattern in OSAS patients, which is not associated with the severity and duration of OSAS. This can have important consequences for the outcome of OSAS patients, especially with regard to the increased risk for developing atherosclerosis and cardiovascular and cerebrovascular diseases. Immediately after the first obstructive apnea causing an SaO2 <85%, a significant variation was observed in the plasma levels of TNF-alpha in OSAS patients compared with those measured before the beginning of polysomnographic recording (P < 0.001). The role played by this further increase in TNF-alpha levels after the obstructive apnea in OSAS patients remains to be established in the light of the pathogenic mechanisms of this sleep disorder.