Concentrations Of RANTES Research Articles

Effect of Neurokinin-1 Receptor Knockdown on the Expression of RANTES in Allergic Rhinitis.

Neurokinin-1 receptor (NK-1R) and normal T cell expressed and secreted (RANTES) have been shown to play important roles in allergic rhinitis (AR). However, whether the regulating effect of NK-1R in AR is achieved via RANTES remains unknown. In the present study, Sprague-Dawley rats were sensitized and challenged with ovalbumin to make AR models. During the challenge period, the rats were treated intranasally with NK-1R-specific small interfering RNA (siRNA) for NKR group, negative siRNA for NCS group, rats in NSAR group and NS group were given saline. The amount of nasal secretion and the numbers of nose rubs and sneezes were measured in each rat. The levels of NK-1R and RANTES in the nasal mucosal tissues were determined through real-time fluorescence quantitative RT-PCR and immunohistochemical staining. The numbers of eosinophils in the collected nasal lavage fluid (NLF) were counted, and the concentration of RANTES in NLF was determined by enzyme-linked immunosorbent assay. Compared with that in the NS group, the expression of NK-1R and RANTES was significantly higher in the nasal mucosa of NSAR and NCS group rats. The sneezing and nose rubbing counts and the amount of nasal secretions were increased significantly in the NSAR and NCS groups. Rats in the NKR group experienced greater relief from AR symptoms than rats in the NSAR and NCS groups. Furthermore, knockdown of NK-1R expression also significantly eliminated RANTES expression and eosinophil infiltration in the nasal mucosa of NKR group rats. For the first time, we show that intranasal treatment with NK-1R-specific siRNA can significantly decrease RANTES expression, AR-related symptoms, and eosinophil inflammation, suggesting that the regulating effect of NK-1R in the development of AR occurs via alteration of RANTES expression.

Molecular Mechanisms of RSV and Air Pollution Interaction: A Scoping Review.

RSV is one of the major infectious agents in paediatrics, and its relationship with air pollution is frequently observed. However, the molecular basis of this interaction is sparsely reported. We sought to systematically review the existing body of literature and identify the knowledge gaps to answer the question: which molecular mechanisms are implied in the air pollutants–RSV interaction? Online databases were searched for original studies published before August 2022 focusing on molecular mechanisms of the interaction. The studies were charted and a narrative synthesis was based upon three expected directions of influence: a facilitated viral entry, an altered viral replication, and an inappropriate host reaction. We identified 25 studies published between 1993 and 2020 (without a noticeable increase in the number of studies) that were performed in human (n = 12), animal (n = 10) or mixed (n = 3) models, and analysed mainly cigarette smoke (n = 11), particulate matter (n = 4), nanoparticles (n = 3), and carbon black (n = 2). The data on a damage to the epithelial barrier supports the hypothesis of facilitated viral entry; one study also reported accelerated viral entry upon an RSV conjugation to particulate matter. Air pollution may result in the predominance of necrosis over apoptosis, and, as an effect, an increased viral load was reported. Similarly, air pollution mitigates epithelium function with decreased IFN-γ and Clara cell secretory protein levels and decreased immune response. Immune response might also be diminished due to a decreased viral uptake by alveolar macrophages and a suppressed function of dendritic cells. On the other hand, an exuberant inflammatory response might be triggered by air pollution and provoke airway hyperresponsiveness (AHR), prolonged lung infiltration, and tissue remodeling, including a formation of emphysema. AHR is mediated mostly by increased IFN-γ and RANTES concentrations, while the risk of emphysema was related to the activation of the IL-17 → MCP-1 → MMP-9 → MMP-12 axis. There is a significant lack of evidence on the molecular basics of the RSV–air pollution interaction, which may present a serious problem with regards to future actions against air pollution effects. The major knowledge gaps concern air pollutants (mostly the influence of cigarette smoke was investigated), the mechanisms facilitating an acute infection or a worse disease course (since it might help plan short-term, especially non-pharmacological, interventions), and the mechanisms of an inadequate response to the infection (which may lead to a prolonged course of an acute infection and long-term sequelae). Thus far, the evidence is insufficient regarding the broadness and complexity of the interaction, and future studies should focus on common mechanisms stimulated by various air pollutants and a comparison of influence of the different contaminants at various concentrations.

Changes in the Synovial Fluid Cytokine Profile of the Knee Between an Acute Anterior Cruciate Ligament Injury and Surgical Reconstruction

Background: Changes in the intra-articular inflammatory state during the immediate period after an acute anterior cruciate ligament (ACL) rupture are not well defined. Purpose: To evaluate changes in the concentration of select proinflammatory and anti-inflammatory synovial fluid cytokines during the interval between an ACL injury and surgical reconstruction. Study Design: Descriptive laboratory study. Methods: In patients with an acute ACL injury, a synovial fluid sample was obtained from the injured knee during the initial office visit within 2 weeks of the inciting traumatic event. An additional synovial fluid sample was collected at the time of ACL reconstruction just before the surgical incision. Synovial fluid samples from both the acute injury and the surgery time points were processed with a protease inhibitor, and the concentrations of 10 cytokines of interest were measured using a multiplex magnetic bead immunoassay. The primary outcome was the change in cytokine concentrations between time points. Results: A total of 20 patients with a mean age of 30.2 ± 8.3 years were included. The acute injury synovial fluid samples were collected at 6.6 ± 3.8 days after the injury. The surgical synovial fluid samples were collected at 31.6 ± 15.6 days after the acute injury samples. Based on a series of linear mixed-effects models to control for the effect of concomitant meniscal injuries and by-patient variability, there was a statistically significant increase in the concentrations of RANTES and bFGF and a statistically significant decrease in the concentrations of IL-6, MCP-1, MIP-1β, TIMP-1, IL-1Ra, and VEGF between time points. Conclusion: This study demonstrates the ongoing alterations in the intra-articular microenvironment during the initial inflammatory response in the acute postinjury period. We identified 6 synovial fluid cytokines that significantly decreased and 2 that significantly increased between the first clinical presentation shortly after the injury and the time of surgery 1 month later. Clinical Relevance: This study describes the molecular profile of the inflammatory changes between the time of an acute ACL injury and the time of surgical reconstruction 1 month later. A greater understanding of the acute inflammatory response within the knee may be helpful in identifying the optimal timing for a surgical intervention that balances the risk of chondral damage with the likelihood of successful, well-healed reconstruction.

Association between aqueous humor cytokines and postoperative corneal endothelial cell loss after Descemet stripping automated endothelial keratoplasty

This study measured the intraoperative anterior aqueous humor concentrations of various cytokines during corneal endothelial transplantation and searched for relationships between these concentrations and postoperative corneal endothelial cell (CEC) depletion. We recruited 30 consecutive patients who underwent corneal endothelial transplantation with Descemet's stripping automated endothelial keratoplasty (DSAEK) at Tohoku University Hospital between February 2014 and July 2017. During surgery, we obtained aqueous humor samples and later measured the concentrations of 27 cytokines with a Multiplex Bead Assay (Bio-Plex Pro). We counted CECs 1, 6 and 12 months after surgery, and used Spearman's rank correlation coefficient to identify relationships between CEC depletion and the concentrations of detected cytokines. The loss of CECs 1-6 months after surgery was significantly correlated with IL-7, IP-10, MIP-1a and MIP-1b concentrations (-0.67, -0.48, -0.39, and -0.45, respectively, all P <0.01). CEC loss 1-12 months after surgery was significantly correlated with IL-1b, IL-7, IP-10 and RANTES concentrations (-0.46, -0.52, -0.48, and -0.43, respectively). Multiple regression analysis showed that IL-7 concentration was significantly associated with CEC loss 1-6 months after surgery (b = -0.65, P < 0.01) and IP-10 concentration was associated with CEC loss 1-12 months after surgery (β = -0.38, P < 0.05). These results suggest that not only inflammatory cytokines but also IL-7, a cytokine related to lymphocytes, may be involved in the depletion of CECs after DSAEK, particularly depletion that occurs relatively early.

Abstract TMP98: Increased Fractalkine and Decreased RANTES Concentrations Predict Progression of Carotid Stenosis Severity at Twenty Months

Introduction: Studies have demonstrated that progression of carotid stenosis severity in asymptomatic patients is associated with increased stroke risk. Identifying stenosis progression mechanisms would improve risk prediction and development of novel targeted treatments. We now examine the association between soluble mediators of inflammation, cell adhesion, angiogenesis and coagulation and progression of stenosis severity in asymptomatic carotid stenosis. Methods: Asymptomatic patients with 50-79% carotid stenosis were enrolled and carotid Doppler surveillance performed every 6-12 months. Plasma was obtained at baseline for measurement of 50 plasma biomarkers of inflammation, cell adhesion, and angiogenesis. Carotid stenosis progression was confirmed by blinded adjudication. Variables associated with progression of stenosis severity (p&lt;0.15) were included in multivariate analysis. Variables retained as significant were included in cox proportional hazard analysis. Results: We enrolled 108 patients (96% male, 34% smokers, average HgA1c 6.6% and average LDL 86 mg/dL). Stenosis severity progressed in 14 (13%) over 20 ± 11 months. Fractalkine (p=0.018), IL-7 (p=0.087), IL-18 (p=0.087), PAI1 (p=0.0871), IL-13 (p=0.0939), and RANTES (p=0.0097) were included in multivariate analysis. Fractalkine (OR = 5.5, p=0.0157) and RANTES (OR = 0.133, p=0.0127) were retained in the final model. Fractalkine concentrations ≥16.9 pg/ml yielded a HR of 4.67 (95% CI 1.3, 16.8; p=0.0093) and RANTES concentrations ≥430 pg/ml yielded a HR of 0.16 (95% CI 0.036, 0.728; p=0.0121) for stenosis progression. Conclusions: Our results show that increased Fractalkine and decreased RANTES concentrations predicted carotid stenosis severity progression at 20 months. Fractalkine is increased in human coronary and carotid artery plaques and prolongs survival of monocytes/macrophages contributing to atherosclerosis progression in Apo E -/- mice. RANTES binds endothelial CCR receptors facilitating migration of T cells and monocytes into the intima. Decreased RANTES levels have been linked to adverse coronary artery disease outcomes. Further study to clarify the role of Fractalkine and RANTES in atherosclerosis progression is warranted.

1. Comparison of serum cytokine concentrations in patients with acute sciatica secondary to lumbar disc herniation choosing surgery with those choosing nonoperative treatment

BACKGROUND CONTEXT The interpretation of research studies comparing clinical outcomes from surgical and nonoperative treatment of patients with acute sciatica secondary to herniated nucleus pulposus (AS/ HNP) remain controversial. Recent studies have concluded that a subset of AS/HNP patients have identifiable biological characteristics that may predict favorable clinical nonoperative treatment outcomes. The mechanism of spinal nerve root injury associated with AS/HNP is mediated at least in part, through an acute inflammatory response that involves the up regulation of specific inflammatory cytokines (eg, TNFα, IL-1β, IL-8 and RANTES). Serum concentrations of these key cytokines measured at standardized points in the clinical course of AS/HNP patients have potential early predictive value in determining favorable clinical outcomes from nonoperative care. PURPOSE To compare serum concentrations and patterns of up regulation of TNFα, IL-1β, IL-8 and RANTES in AS/HNP patients who elected to have surgery with those who chose nonoperative care. STUDY DESIGN/SETTING Prospective cohort. PATIENT SAMPLE Inclusion: AS/HNP of less than 16 weeks duration who declined a selective nerve root steroid injection; spinal nerve root motor score of >3/5; McCulloch score of 5/5 Exclusion: red flag condition; prior lumbar surgery; other active inflammatory diseases. OUTCOME MEASURES Serum concentrations and patterns of up regulation of TNFα, IL-1β, IL-8 and RANTES at baseline, 6, 12 and 24 weeks post baseline. METHODS Patients meeting the inclusion and exclusion criteria were recruited to the study through an Acute Disc Clinic in a hospital-based spine program outpatient clinic. After providing informed consent, blood samples were obtained by venipuncture (baseline) and at 6, 12 and 24 weeks post baseline. Serum cytokine concentrations were measured by ELISA immunoassay. Patient preference to have surgery or nonoperative treatment was recorded. Patient use of oral medications, including NSAIDS was recorded at each data collection date. Research ethics approval was obtained. RESULTS Forty patients were enrolled over a period of 18 months, with 24 electing to undergo laminectomy discectomy surgery. Time of surgery from baseline ranged from 11-14 weeks. 6/40 patients reporting taking oral NSAIDS for less than one week in total for the duration of the study. At 24 weeks post baseline, 8/40 patients reported persisting thigh symptoms and 2/40 patients reported symptoms below the knee and had positive nerve root tension signs. Degree of up regulation of serum levels concentrations of TNFα, IL-1β, IL-8 and RANTES concentrations (pg/ml) at each data collection point were compared to 24-week levels for each patient. In patients 22/24 electing to undergo surgery, RANTES and IL-1β concentrations were increased 10-14fold compared to asymptomatic (ie, 24 week) levels, and in 13/16 patients by 5-7fold in patients choosing nonoperative care. TNFα concentrations were increased by 3-5fold in both surgical and nonoperative groups at baseline. Elevated concentrations of RANTES and IL-1β were maintained or were increased at 6 weeks post baseline in the same 22/24 patients undergoing surgery and diminished by an average of 28% in the same 13/16 patients electing to have nonoperative treatment. CONCLUSIONS In this study population, patients with highly up regulated baseline serum concentrations of RANTES and IL-1β that did not diminish at 6 weeks post baseline were associated with patient treatment choice to have surgery. TNFα serum concentrations were not associated with patient treatment preference. A larger scale study is required to further investigate these findings. Funded by a research grant from the National Institutes of Health, Bethesda, MD, USA. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Retinopathy severity correlates with RANTES concentrations and CCR 5-positive microvesicles in diabetes.

RANTES regulates leukocyte recruitment to areas affected by the inflammatory process. Microvesicles (MVs) belong to a subpopulation of extracellular vesicles and show proangiogenic potential by transferring bioactive molecules to target cells. the aim of this study was to determine the relationship between circulating proangiogenic factors (MVs and RANTES) and diabetes complications in patients with different severities of diabetic retinopathy (DR). CCR5 (CD195) receptors transported by annexin V-labeled MVs were also investigated. Diabetic patients (n = 61), among whom 35 had confirmed DR classified according to guidelines, and controls (n = 25) were included. MVs were isolated by centrifugation and analyzed using flow cytometry, RANTES was assessed by ELISA. the study group differed from the control group with respect to BMI, age, heart rate and systolic blood pressure. Additionally, glucose and creatinine concentrations were significantly increased: 5.30 [5.09-5.62] vs. 9.38 [7.48-11.55] (p <0.0001) mmol/l and 74.59 [64-84] vs. 89.00 [77.11-105.44] μmol/l (p = 0.0005), respectively. RANTES concentrations were significantly increased in diabetic patients compared to those of controls (15.5 (9.7-18.1) vs. 8.9 (0.9-14.6) μg/ml (p = 0.011)), and RANTES concentration significantly increased with respect to nonproliferative DR progression. Moreover, the number of CCR5-positive MVs was significantly increased in patients with heavy nonproliferative diabetic retinopathy (HNPDR) compared to those with so nonproliferative DR (SNPDR): 1178 [836-2254] vs. 394 [275-799] counts/μl. Correlation of RANTES concentrations with the stage of nonproliferative DR and the statistically significant dependence of CCR5-positive MVs with disease progression suggest that MVs and RANTES can be considered new biomarkers.

The Regulation of Seventeen Inflammatory Mediators are Associated with Patient Outcomes in Severe Fever with Thrombocytopenia Syndrome

Severe fever with thrombocytopenia syndrome (SFTS) as an emerging infection disease results in high morbidity and mortality in China. In this study, the circulating levels of 36 inflammatory mediators in 33 SFTS patients on days 3–7, 8–12 and 13–20 post-illness were measured by a multiplex Luminex® system dynamically. Among the patients, 15 severe patients recovered, 11 severe patients died within three weeks. We found IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, eotaxin, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β and fractalkine were significantly upregulated in SFTS patients. Elevated IL-15 and eotaxin in SFTS patients were reported firstly. The highest levels of pro-inflammatory and anti-inflammatory cytokines coexisted in fatal patients during the first week. Inflammatory mediators remained high levels when death occurred in fatal patients, they were recovered within three weeks in nonfatal patients. Our results showed the occurrence of inflammatory storm in SFTS patients were associated with the severity of SFTS. RANTES and PDGF were down regulated and remained significantly lower levels in fatal patients throughout the course of disease, the concentrations of RANTES and PDGF were remarkably positively correlated with the platelet count. Our results demonstrated that dysregulated inflammatory response was associated with disease pathogenesis and mortality in SFTS patients.

The selective biomarker IL-8 identifies IFTA after kidney transplantation in blood cells

Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers in blood cells and serum may serve as diagnostic tools but studies with high patient numbers and differential groups are rare. We validated the potential value of several markers on mRNA level in blood cells and serum protein level in 166 samples from kidney transplanted patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection (UTI), IFTA, antibody-mediated rejection (ABMR), and T-cell-mediated rejection (TCMR) applying RT-PCR and ELISA. The mRNA expression of RANTES, granulysin, granzyme-B, IP-10, Mic-A and Interferon-γ in blood cells did not distinguish specifically between the different pathologies. We furthermore discovered that the mRNA expression of the chemokine IL-8 is significantly lower in samples from IFTA patients than in samples from patients with stable graft function (p<0.001), ABMR (p<0.001), Borderline (BL) TCMR (p<0.001), tubulo-interstitial TCMR (p<0.001) and vascular TCMR (p<0.01), but not with UTI. Serum protein concentrations of granzyme-B, Interferon-γ and IL-8 did not differ between the patient groups, RANTES concentration was significantly different when comparing UTI and ABMR (p<0.01), whereas granulysin, Mic-A and IP-10 measurement differentiated ongoing rejection or IFTA processes from stable graft function but not from each other.The measurement of IL-8 mRNA in blood cells distinguishes clearly between IFTA and other complication after kidney transplantation and could easily be used as diagnostic tool in the clinic.

Selected CC and CXC chemokines in children with atopic asthma.

IntroductionThere are only limited data on CC and CXC chemokines regulation in children with asthma.AimWe compared the serum profile of selected CC and CXC chemokines in patients with atopic asthma and healthy children.Material and methodsSerum concentration of CC chemokines RANTES, MCP-1, and CXC chemokines IP-10, MIG, IL-8, RANTES was measured using cytometric bead array in 44 children with atopic asthma and 17 healthy subjects.ResultsThe concentration of RANTES was significantly higher and the MIG level was lower in all children with asthma as compared to their control counterparts. We observed increased RANTES and decreased MIG levels also in patients with stable asthma when compared with children in the control group. The IP-10 concentration was similar between the whole asthma group and healthy controls, while significantly increased levels of this chemokine in acute asthma have been observed when compared to stable asthma. For MCP-1 and IL-8, the serum concentration was similar in all compared groups. The MIG concentration correlated positively with IP-10, IL-8, and CRP levels and negatively with the eosinophil count. A negative correlation between the IP-10 and eosinophil count and a negative correlation between FEV1 and IP-10 were found.ConclusionsAn increased serum RANTES level in children with asthma may result in enhancement of Th2 lymphocyte recruitment into the airway. A decreased expression of Th1 chemokine MIG in children with stable asthma may contribute to a diminished antagonizing effect on Th2 cytokine production and hence intensify Th2 predominance. An increased IP-10 level in children during an asthma attack suggest that this chemokine is a serological marker of disease exacerbation.

Injectable Progestin-Only Contraception is Associated With Increased Levels of Pro-Inflammatory Cytokines in the Female Genital Tract.

Genital inflammatory changes may be a mechanism of increased HIV risk among injectable progestin-only contraception (IPC) users. We conducted a cross-sectional analysis of 376 Kenyan and South African women. Genital cytokines and secretory leukocyte peptidase inhibitor concentrations in a reference population were compared to IPC users and women with reproductive tract infections. No significant variability in marker concentrations was observed by age or site. Depot medroxyprogesterone acetate (DMPA) users had significantly higher MIP-1α, MIP-1β, IL-6, IL-8, IP-10, and RANTES concentrations. Norethisterone oenanthate users had significantly higher IL-6, IL-8, and RANTES concentrations. Women with sexually transmitted infections had variable inflammation, and women with bacterial vaginosis exhibited a mixed profile of up and downregulation. The finding of substantial mucosal inflammation among DMPA users provides evidence which, combined with the results of prior studies, suggests that DMPA may create an immune environment conducive to HIV target cell recruitment and inhibitory for antiviral activity.

Thrombocytopenia May Mediate Disease Severity in Plasmodium falciparum Malaria Through Reduced Transforming Growth Factor Beta-1 Regulation of Proinflammatory and Anti-inflammatory Cytokines.

Transforming growth factor beta-1 (TGF-β1) is an important regulator of inflammation. Platelets are a major source of TGF-β1 and are reduced in severe malaria. However, the relationships between TGF-β1 concentrations and platelet counts, proinflammatory and anti-inflammatory cytokine and chemokine concentrations and disease severity in malaria have not been characterized. Platelet counts and serum concentrations of TGF-β1, interleukin-1beta (IL-1β), IL-6, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and RANTES were measured at the time of presentation in Ugandan children with cerebral malaria (CM, n = 75), uncomplicated malaria (UM, n = 67) and healthy community children (CC, n = 62). TGF-β1 concentrations decreased with increasing severity of disease [median concentrations (25th, 75th percentile) in ng/mL in CC, 41.4 (31.6, 57.4); UM, 22.7 (14.1, 36.4); CM, 11.8 (8, 21); P for trend < 0.0001]. In children with CM or UM, TGF-β1 concentrations correlated positively with platelet count (CM, P < 0.0001; UM, P = 0.0015). In children with CM, TGF-β1 concentration correlated negatively with IFN-γ, IL-6 and IL-10 and positively with RANTES concentrations (all P < 0.01). TGF-β1 concentration was not associated with death or adverse neurologic or cognitive outcomes in children with CM. TGF-β1 concentrations decrease with increasing Plasmodium falciparum disease severity. In CM, thrombocytopenia correlates with decreased TGF-β1, and decreased TGF-β1 correlates with cytokine/chemokine changes associated with increased disease severity and death. Thrombocytopenia may mediate disease severity in malaria through reduced TGF-β1-mediated regulation of cytokines associated with severe disease.

Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness.

Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments.

The role of chemokine and non-chemokine factors in pain-related complaints in patients with endometrial cysts.

Endometriosis is a chronic disease manifested as peritoneal endometrial implants and adhesions, as well as endometrial cysts, with pain as the dominant component. The aim of the study was to evaluate the role of chemokine (MCP-1, MCP-2, MIP-1, MIP-1 and RANTES) and non-chemokine (urocortin, ghrelin, and leptin) factors in the intensity of pelvic pain in women with endometrial cysts. A total of 86 women, aged 18-38, treated laparoscopically between September 2009 and November 2012, due to adnexal changes, i.e. endometrial cysts and mature teratomas, were recruited for the study. On a numeric rating scale, i.e. PSS (Pain Sensation Scale--according to Johnson), the patients rated pain intensity. The level of pain-related stress was investigated with the Pain Distress Scale (PDS, according to Johnson). Medians for MCP-1, MCP-2, MIP-1, MIP-1 and RANTES concentrations were not statistically significantly different. The respondents rated pain intensity during menses as 6 and 3 points in the E and T groups, respectively (6 vs. 3 points; p=0.001). Statistically significant differences were also observed for pain intensity during work (apart from menses), (2 vs. 2 points, p=0,014) and during sexual intercourse (apart from menses) (3 vs. 1 points, p=0.006). Pain-related stress levels were higher in the T group as compared to the E group (3 vs. 5 points; p=0.007). It seems safe to conclude that chemokines and leptin may play a significant role in the occurrence of pain complaints among women with endometrial cysts. Further research might result in implementation of new treatment methods for pain management, especially in terms of pharmacotherapy.

Viral Specific Factors Contribute to Clinical Respiratory Syncytial Virus Disease Severity Differences in Infants.

BackgroundThere is a wide range of severity of respiratory syncytial viral (RSV) disease in previously healthy infants. Host factors have been well demonstrated to contribute to disease severity differences. However the possibility of disease severity differences being produced by factors intrinsic to the virus itself has rarely been studied.MethodsLow-passage isolates of RSV collected prospectively from infants with different degrees of RSV disease severity were evaluated in vitro, holding host factors constant, so as to assess whether isolates induced phenotypically different cytokine/chemokine concentrations in a human lung epithelial cell line. Sixty-seven RSV isolates from previously healthy infants (38 hospitalized for acute RSV infection (severe disease) and 29 never requiring hospitalization (mild disease)) were inoculated into A549, lung epithelial cells at precisely controlled, low multiplicity of infection to mimic natural infection. Cultures were evaluated at 48 hours, 60 hours, and 72 hours to evaluate area under the curve (AUC) cytokine/chemokine induction.ResultsCells infected with isolates from severely ill infants produced higher mean concentrations of all cytokine/chemokines tested (IL-1α, IL-6, IL-8 and RANTES) at all-time points tested. RSV isolates collected from infants with severe disease induced significantly higher AUCIL-8 and AUCRANTES secretion in infected cultures than mild disease isolates (p=0.028 and p=0.019 respectively). IL-8 and RANTES concentrations were 4 times higher at 48 hours for these severely ill infant isolates. Additionally, 38 isolates were evaluated at all-time points for quantity of virus. RSV concentration significantly correlated with both IL-8 and RANTES at all-time points. Neither cytokine/chemokine concentrations nor RSV concentrations were associated with RSV subgroup.DiscussionInfants’ RSV disease severity differences may be due in part to intrinsic viral strain-specific characteristics.

Increased circulating RANTES in type 2 diabetes.

The pro-atherogenic role of RANTES, a chemokine expressing pleiotropic activities, in the course of type 2 diabetes-related atherosclerosis has been well documented. However, it is not known which of the diabetes-related factors primarily influence serum RANTES levels in patients with type 2 diabetes. Our aim was to investigate relationships between several factors known to be related to an increased risk of atherosclerosis and serum RANTES levels in type 2 diabetic patients. A total of 168 subjects were examined, which included 138 patients with type 2 diabetes and 30 non-diabetic controls. Measurements of venous, fasting, plasma glucose, HbA1c, lipid profile, 1,5-anhydro-D-glucitol (1,5-AG) plasma levels, homocysteine and the fasting, serum C-peptide levels were performed. Serum concentrations of RANTES were assayed using BD(TM) Cytometric Bead Array tests. Peripheral insulin resistance was expressed according to a new index defined by Ohkura et al. RANTES levels in type 2 diabetic patients correlated with 1,5-AG, fasting glycaemia, HbA1c and the Ohkura index. Multivariate regression analysis was performed taking into consideration several factors related to the inflammatory process and atherosclerosis, namely the patient's age, diabetes duration, waist circumference, 1,5-AG, HbA1c, lipid profile parameters, serum homocysteine levels and Ohkura index, as independent variables potentially influencing serum RANTES levels in type 2 diabetic patients. It is shown that RANTES concentrations in the serum is primarily dependent upon 1,5-AG plasma levels. Our results suggest that increased serum levels of RANTES in type 2 diabetic patients are closely related to postprandial (acute) hyperglycaemia.

Abstract W MP32: Localized Increase of Chemokines in the Lumen of Human Cerebral Aneurysms

Introduction: Inflammation may play an important role in the formation and rupture of cerebral aneurysms. Chemokines act as chemoattractants for leukocytes directing them toward sites of tissue inflammation. The purpose of this study was to determine whether chemokines and chemoattractant cytokines were increased in the lumen of human cerebral aneurysms. Methods: The concentrations of chemokines and other inflammatory molecules in blood samples drawn from the lumen of human cerebral aneurysms of 16 consecutive patients (harboring 18 aneurysms) were compared with blood samples from femoral arteries of the same patients. Specifically, the concentrations of the following molecules were determined: RANTES, monokine-induced-by-gamma-interferon (MIG), interferon-gamma-induced protein-10 (IP-10), eotaxin, interleukin (IL) 1-beta, IL 1 Receptor Antagonist, IL2, IL2 Receptor, IL4, IL5, IL6, I7, IL8, IL10, IL12, IL13, IL15, IL17, vascular endothelial growth factor, granulocyte colony stimulating factor, epidermal growth factor, basic fibroblast growth factor, granulocyte monocyte colony stimulating factor, tumor necrosis factor-alpha, interferon-alpha, interferon-gamma, macrophage inflammatory protein 1 alpha, macrophage inflammatory protein-1-beta, and monocyte chemoattractant protein-1 (MCP-1). Results: The mean plasma concentration of RANTES, MIG, IP-10, eotaxin, IL 8, and IL17 was significantly higher in samples taken from cerebral aneurysms compared with femoral arteries. In contrast, plasma concentrations of all remaining inflammatory molecules (except IL6) that were tested did not differ between cerebral aneurysms and femoral arteries. For unruptured aneurysms, there was a significantly higher mean plasma concentration of monocyte chemoattractant protein-1,RANTES, MIG, IP-10, eotaxin, IL8, and IL17 in samples obtained from cerebral aneurysms. Conclusions: High plasma concentrations of chemokines (monocyte chemoattractant protein-1, RANTES, MIG, IP-10, and eotaxin) and chemoattractant cytokines (IL8 and IL17) were found in the lumen of human cerebral aneurysms. These findings suggest that there may be an active recruitment of inflammatory cells into the aneurysm wall that may be exploited therapeutically.

Intensive Lifestyle Modification Reduces Lp-PLA2 in Dyslipidemic HIV/HAART Patients

Patients with dyslipidemia associated with HIV-1 infection and highly active antiretroviral therapy (HAART) have elevated levels of Lp-PLA2 and CCL5/regulated on activation, normal T-cell expressed and secreted (RANTES), which may increase the risk of cardiovascular disease. This study aimed to determine whether an intensive diet and exercise (D/E) program, independently or combined with fenofibrate or niacin, could reduce Lp-PLA2 or RANTES. Patients with hypertriglyceridemic HIV on stable HAART (n = 107) were randomized to one of five interventions: 1) usual care, 2) D/E with placebos, 3) D/E with fenofibrate and placebo, 4) D/E with niacin and placebo, or 5) D/E with fenofibrate and niacin for 24 wk. Lp-PLA2 and RANTES concentrations were measured in fasting plasma samples at baseline and postintervention. General linear models were used to compare Lp-PLA2 and RANTES levels between the five groups postintervention, controlling for baseline levels, age, body mass index, CD4 T-cell count, viral load, duration of infection, and HAART. At baseline, fasting plasma Lp-PLA2 (388.5 ± 127.5 ng·mL) and RANTES (43.8 ± 25.5 ng·mL) levels were elevated when compared with healthy controls. Posttreatment Lp-PLA2 mass was lower in patients who received D/E only (323.0 ± 27.2 ng·mL), D/E plus fenofibrate (327.2 ± 25.9 ng·mL), and D/E plus niacin (311.1 ± 27.8 ng·mL) when compared with patients receiving usual care (402.2 ± 25.3 ng·mL). RANTES concentrations were not significantly affected by any intervention. Elevated plasma Lp-PLA2 mass can be reduced by an intensive D/E program in patients with HIV/HAART-associated dyslipidemia. RANTES is elevated but is not reduced by lifestyle modification, fenofibrate, or niacin.

Late-preterm cesarean delivery and chemokines concentration in the umbilical cord blood of neonates

Objective: The objective of the study was to investigate whether concentrations of chemokines in the umbilical cord blood of neonates are affected by delivery via cesarean section. Study design: Umbilical cord blood was obtained from 116 singleton late-preterm and full-term neonates without infections, born to healthy pregnant women. Concentrations of chemokines – MIP-1α (CCL3), MIP-1β 1 (CCL4), RANTES (CCL5), GRO-α (CXCL1) and ENA-78 (CXCL5) – were measured by ELISA. Logistic regression was used to investigate regression relationships between the occurrence of neonatal chemokines concentrations in umbilical cord blood and mode and time of delivery. Results: Concentrations of CXC chemokines in late-preterm neonates were the same as those in term neonates. RANTES concentrations in late-preterm cord blood were significantly lower than concentrations in term cord blood. Concentrations of the CC chemokine – RANTES (CCL5) – were noted to be lower in neonates born to cesarean section than in neonates born vaginally. Any anesthetic taken by the mothers during cesarean section did not affect CC chemokine production in the cord blood of full-term neonates. In a logistic regression model including gestational age as a variable, late-preterm delivery was associated with RANTES concentrations (OR = 3.8). After adjustment for variable mode of delivery in regression model, RANTES concentration (OR = 4.75). Conclusion: Both late-preterm and cesarean delivery are essential risk factors of low RANTES (CCL5) concentrations in the umbilical cord blood.

Sphingosine kinase inhibition exerts both pro- and anti-atherogenic effects in low-density lipoprotein receptor-deficient (LDL-R−/−) mice

Sphingosine 1-phosphate (S1P), a lysosphingolipid associated with high-density lipoprotein (HDL), contributes to the anti-atherogenic potential attributed to this lipoprotein. This study examined whether a reduction of S1P plasma levels affects atherosclerosis in a murine model of disease. LDL-R(-/-)mice on Western diet were given ABC294640, an inhibitor of sphingosine kinase (SphK) for 16 weeks. ABC294640 decreased plasma S1P by approximately 30%. However, ABC294640 failed to affect atherosclerotic lesion formation. Plasma triglycerides were reduced whereas total and HDL-cholesterol remained unchanged in course of ABC294640 treatment. ABC294640 increased plasma interleukin (IL)-12p70 and RANTES concentration as well as IL-12p70, RANTES and interferon (IFN)-γ production by peritoneal cells and this was paralleled by enhanced activity of peritoneal and spleen dendritic cells as evidenced by up-regulation of CD86 and MHC-II on CD11c(+) cells. As a consequence, increased T-cell activation was noted in ABC294640-treated mice as indicated by enhanced CD4(+) splenocyte proliferation, IFN-γ and IL-2 production, and CD69 expression. Concomitantly, however, ABC294640 treatment redistributed CD4(+) and CD8(+) cells from blood to lymphatic organs and reduced T-cell number within atherosclerotic lesions. In addition, plasma sVCAM-1, sICAM-1, and MCP-1 levels as well as in vivo leukocyte adhesion and CCL19-induced T-cell penetration into peritoneum were lower in ABC294640-treated animals. In vitro experiments demonstrated reduced VCAM-1 and ICAM-1 expression and lymphocyte adhesion to endothelial cells exposed to ABC294640. In conclusion, treatment with SphK inhibitor leads to both pro- and anti-atherogenic effects in LDL-R(-/-) mice. As a consequence, SphK inhibition fails to affect atherosclerosis despite significant S1P reduction in plasma.