interleukin-8 and Venous-Thrombosis

During the past decade, the role of inflammation in the pathophysiology of arterial thrombosis has been elucidated. However, comparatively little is known about the relationship between inflammation and venous thrombosis. The aim of this study was to perform a systematic review of clinical studies that have examined the association between inflammation and venous thrombosis, specifically: (1) the value of inflammatory markers in predicting the future development of venous thrombosis; (2) test characteristics of markers of inflammation in the diagnosis of acute venous thrombosis; and (3) effect of venous thrombosis on blood levels of inflammatory markers. Using keywords venous thrombosis, venous thromboembolism, inflammation, acute phase markers, C-reactive protein (CRP), interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1, PubMed and Medline computerized databases were searched for English language articles published after 1980. Search results were restricted to clinical studies in humans that used study designs that were appropriate to address the above objectives. Results show that plasma CRP levels do not appear to predict risk of future venous thrombosis (two studies; N = 41,308). Four studies (N=562) have examined the utility of plasma CRP in the diagnosis of venous thrombosis; pooled positive and negative predictive values were 53% (95% CI:47%,59%) and 85% (95% CI: 81%, 89%), respectively. A two- to six-fold increase in the risk of deep vein thrombosis (DVT) is associated with elevations in plasma levels of CRP, IL-6, IL-8, MCP-1 or TNF-alpha (three studies). We can conclude that the nature of the relationship between inflammation and clinical venous thrombosis is not yet established. CRP does not appear to be useful in predicting future venous thrombosis or in the diagnosis of acute venous thrombosis. While several markers of inflammation are elevated in acute venous thrombosis, further research is needed to determine the precise relationship between these markers and venous thrombosis. The identification and elucidation of inflammatory markers relevant to venous thrombosis could provide targets for future therapy.

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Chemokine CCL2; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Odds Ratio; Venous Thrombosis

This study was to investigate the efficacy of low molecular weight heparin (LMWH) therapy in patients with spinal trauma after part concentrated screw (PCS) pedicle screw surgery (PSS) and its influence on blood parameters and the incidence of deep venous thrombosis. Prospectively, 36 patients with spinal trauma who underwent PSS were randomly divided into an experimental group (n = 18) and a control group (n = 18). The experimental group was treated with LMWH after the operation. Changes in the vascular endothelial function, inflammatory factors and other blood indexes, and the incidence of deep venous thrombosis in lower extremities were compared between the two groups before and after the surgery. Compared to pre-surgery, the levels of endothelin (ET) and tissue plasminogen activator (tPA) in the experimental group decreased significantly after surgery (all P < 0.001), while the levels of ET increased and tPA decreased significantly in the control group (all P < 0.001). In addition, compared with pre-surgical levels, interleukin-8 (IL-8), IL-6 and procalcitonin (PCT) decreased significantly in the experimental group after surgery while there was a significant increase in these cytokines in the control group (all P < 0.001), with a significant difference in the cytokine levels between the two groups post-surgery (P < 0.01). After the surgery, plasma viscosity, erythrocyte electrophoresis time and platelet aggregation rate in the control group were significantly increased from pre-surgery levels (all P < 0.001), and these levels were also significantly higher than in the experimental group (P < 0.01). The D-dimer (D-D) level in both groups also increased significantly after surgery (all P < 0.001), and the level post-surgery was significantly higher in the experimental group as compared to the control group (P < 0.01). Finally, the incidence of deep venous thrombosis in the experimental group was significantly lower than in the control group (P < 0.05). LMWH is beneficial in reducing the degree of hypercoagulability, hyperviscosity and inflammatory reaction in patients with spinal trauma who underwent PSS. It also effectively reduced the occurrence of deep vein thrombosis in lower limbs after surgery. Thus, it is a candidate for further clinical development.

Topics: Adult; Anticoagulants; Blood Coagulation; Bone Screws; Endothelins; Endothelium, Vascular; Erythrocytes; Female; Heparin, Low-Molecular-Weight; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Membrane Proteins; Pedicle Screws; Procalcitonin; Prospective Studies; Spinal Injuries; Thrombosis; Venous Thrombosis; Viscosity

Recently, microRNAs (miRNAs) have been demonstrated to play important roles in the cardiovascular system, including heart, blood vessels, plasma, and vascular diseases. Deep vein thrombosis (DVT) refers to the formation of blood clot in the deep veins of the human body and is a common peripheral vascular disease. Herein, we explored the mechanism of miR-9-5p in DVT through nuclear factor-κB (NF-κB). The expression of miR-9-5p in DVT rats was measured through the establishment of DVT rat models, followed by the alteration of miR-9-5p and NF-κB p50 in rats through the injection of constructed lentiviral vectors so as to explore the role of miR-9-5p and NF-κB p50 expression in rats. Next, the expression of NF-κB p50 and levels of inflammation-related factors plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-8 (IL-8) were measured after the injection with lentiviral vectors, followed by the assessment of platelet aggregation and TXB2 content. MiR-9-5p was found to be downregulated in DVT rats. Through dual luciferase reporter gene assay, NF-κB p50 was verified as the target gene of miR-9-5p and miR-9-5p could negatively regulate NF-κB p50. MiR-9-5p over-expression decreased the levels of PAI-1, TNF-α, IL-6, and IL-8 and platelet aggregation as well as TXB2 content, thus inhibiting thrombosis. Meanwhile, over-expressed NF-κB p50 could reverse the anti-inflammatory or anti-thrombotic effect of miR-9-5p. In summary, miR-9-5p over-expression can suppress the NF-κB signaling pathway through p50 downregulation, thus alleviating inflammation and thrombosis in DVT rats. MiR-9-5p could serve as a potential therapeutic target for DVT.

Topics: Animals; Gene Expression Regulation; Inflammation; Interleukin-6; Interleukin-8; MicroRNAs; NF-kappa B p50 Subunit; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Protective Agents; Rats; Thromboxane B2; Tumor Necrosis Factor-alpha; Venous Thrombosis

The aim of this study was to analyse the normalization rate of compression ultrasonography after a first episode of proximal deep venous thrombosis (DVT). Patients underwent compressive ultrasound (C-US) examinations during the 3-6 months following the first proximal DVT episode. Normalization rate of compressive ultrasound (C-US) during the follow-up period was 26.4% [95% confidence interval, 16.3-37.3]. Allelic variation in factor XIII gene (Val34Leu) significantly affected the improvement of popliteal residual thrombi (P = 0.019). We also observed a significant negative correlation between D-dimer levels at 3 months and improvement of popliteal residual thrombi (P = 0.016). There was a significant positive correlation between baseline lumen diameter of the femoral thrombi and IL-8 cytokine (P = 0.015). A significant difference was also found between 1 month-tumor necrosis factor (TNF)-α levels and improvement of residual thrombi (P = 0.047). Our results show that normalization after a standard period of anticoagulation is not frequent and procoagulant and inflammatory biomarkers and also some genetic variations might be related to the resolution of thrombosis.

Topics: Adult; Aged; Alleles; Anticoagulants; Biomarkers; Factor XIII; Female; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-8; Male; Middle Aged; Mutation; Polymorphism, Genetic; Popliteal Vein; Risk Factors; Tumor Necrosis Factor-alpha; Ultrasonography; Venous Thrombosis

Proanthocyanidins are abundantly found in grape seeds and have been suggested to inhibit the pathogenesis of systemic diseases. We investigated the antithrombotic effects of proanthocyanidins in a rat model of deep vein thrombosis (DVT) and examined the underlying mechanisms.. DVT was induced in rat model by inferior vena cava (IVC) ligation. Grape seed proanthocyanidins extract (GSPE, 400 mg/kg/d) dissolved in saline (2 mL) was orally administered to the experimental rats. Control rats were administrated saline (2 mL) only. The thrombi were harvested and weighed. The IVC was analyzed histologically and by transmission electron microscopy. The cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Expression of cellular adhesion molecules (CAMs) in thrombi was examined by Western blot.. GSPE significantly reduced thrombus length and weight (P < .01) and protected the integrity of the endothelium. GSPE inhibited thrombogenesis-promoting factors P-selectin, von Willebrand factor, and CAMs, and promoted thrombogenesis-demoting factors CD34, vascular endothelial growth factor receptor-2, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type one motif, member 13). Compared with the control, GSPE significantly lowered the cytokines IL-6 (74.19 ± 13.86 vs 189.54 ± 43.76 pg/mL; P < .01), IL-8 (80.71 ± 21.42 vs 164.56 ± 39.54 pg/mL; P < .01), and TNF-α (43.11 ± 17.58 vs 231.84 ± 84.11 pg/mL; P < .01).. GSPE significantly inhibited the propagation of thrombus induced by IVC ligation in a rat model. The antithrombotic properties of proanthocyanidins are likely to be directly associated with endothelial protection and regeneration, platelet aggregation, and inhibition of inflammatory cell and thrombus adhesion. Thus, proanthocyanidins may have a clinical application in DVT treatment.

Topics: ADAM Proteins; ADAMTS13 Protein; Administration, Oral; Animals; Antigens, CD34; Blotting, Western; Disease Models, Animal; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Fibrinolytic Agents; Interleukin-6; Interleukin-8; Ligation; Male; Microscopy, Electron, Transmission; P-Selectin; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Seeds; Time Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor-2; Vena Cava, Inferior; Venous Thrombosis; Vitis; von Willebrand Factor

The aim of this study was to evaluate the levels of anti-inflammatory interleukin-10 and pro-inflammatory cytokines and their relationship to endothelial function in patients with idiopathic venous thrombosis. Forty-nine eligible patients of both sexes with idiopathic venous thrombosis and 48 matched control subjects were studied. Levels of inflammatory markers were determined. Endothelial function was evaluated by ultrasound measurement of the flow mediated dilatation (FMD) of the brachial artery. Compared to the control group, patients with idiopathic venous thrombosis had significantly lower levels of interleukin-10 1.81 pg/ml (1.53-2.21) versus 2.71 pg/ml (1.84-3.65), p < 0.001. Patients also had increased levels of pro-inflammatory cytokines: interleukin-6 2.37 pg/ml (1.59-4.09) versus 2.03 pg/ml (1.49-2.59), p = 0.025, interleukin-8 3.53 pg/ml (2.94-5.30) versus 2.25 pg/ml (1.77-2.90), p < 0.001. Furthermore, decreased FMD was observed in patients: 5.0% (3.9-6.9) versus 12.7% (10.8-15.6), p < 0.001. FMD was related to levels of interleukin-10 (r = 0.33, p = 0.001) and was inversely related to pro-inflammatory cytokines interleukin-6 (r = -0.34, p = 0.001) and interleukin-8 (r = -0.43, p < 0.001). Patients with idiopathic venous thrombosis have decreased levels of IL-10 and increased levels of pro-inflammatory cytokines. This imbalance indicates that in the stable phase of the disease, patients have an increased systemic inflammatory response. This inflammatory response could be the consequence of the disease, but most probably is involved in the pathogenesis of venous thrombosis.

Topics: Adult; Aged; Biomarkers; Brachial Artery; Case-Control Studies; Down-Regulation; Endothelium, Vascular; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Linear Models; Male; Middle Aged; Slovenia; Tumor Necrosis Factor-alpha; Ultrasonography, Doppler, Pulsed; Vasodilation; Venous Thrombosis

Cytokines increased the risk of venous thromboembolism (VTE) in some case-control studies, but not in a prospective study. Data concerning the role of cytokines in the risk of VTE are limited. We examined in a case-control study the association of VTE and levels of interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) and assessed whether promoter polymorphisms (IL-6 -174GC, IL-8 -251AT, MCP-1 -2518AG) would affect the thrombotic risk and cytokine levels.. The study included 119 patients (94 women) with a first event of VTE aged between 18-60 years, and 126 healthy controls (100 women) matched for age (±5 years). Blood was collected >7 months after the thrombotic event. Odds ratios (ORs) were calculated per increase of cytokines levels by 1 pg/mL.. ORs adjusted for age and sex were 1.520 [95% Confidence Interval (CI) 1.177 - 1.962] for IL-6, 1.095 (95% CI 1.002 - 1.196) for IL-8 and 1.000 (0.988 - 1.012) for MCP-1. With additional adjustment for ethnic composition, body mass index (BMI) and high sensitive C-reactive protein (hs-CRP), risk estimates remained significant for IL-6 and became of borderline statistical significance for IL-8. Polymorphisms did not influence the thrombotic risk and the cytokine levels in study participants.. VTE was associated with IL-6 and IL-8 levels, and for IL-6 this association was independent of BMI and hs-CRP. Thus far, a causal relationship between inflammation and VTE remains to be clarified and more prospective data are warranted.

Topics: Adolescent; Adult; Case-Control Studies; Chemokine CCL2; Cytokines; Female; Genetic Predisposition to Disease; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Venous Thrombosis; Young Adult

During the past decade, the role of inflammation in the pathophysiology of arterial thrombosis has been elucidated. However, little is known about the relationship between inflammation and venous thrombosis. Recently, inflammation has been accepted as a possible mechanism through which different risk factors trigger thrombus formation in veins. The aim of the present study was to investigate the inflammatory markers and their relationship to idiopathic venous thrombosis.. Fourty-nine patients with first idiopathic venous thrombosis and 48 age matched control subjects were included in the study. Patients were studied 2-4 months after the acute event. Patients and control subjects did not differ in the classical risk factors of atherosclerosis, except in body mass index. In both groups, blood markers of inflammation, namely high sensitive C-reactive protein (hs CRP), interleukins (IL-6, IL-8) and tumour necrosis factor alpha (TNF-a), and circulating markers of endothelial dysfunction/damage namely von Willebrand factor (vWF), P-selectin and the vascular adhesion molecule (VCAM-1) were measured.. In comparison to healthy subjects patients had significantly higher levels of inflammatory markers: hs CRP: 2.58 mg/L (1.37-6.61), vs. 1.67 mg/L (0.97-3.24) P=0.044, IL-6: 2.37 pg/mL (1.59-4.10), vs. 2.03 pg/mL (1.45-2.59), P=0.025, IL-8: 3.53 pg/mL (2.94-5.3), vs. 2.25 pg/mL (1.77-2.90) P < or = 0.0001. However, concentrations of TNF-a did not differ significantly between the groups. Also in patients higher levels of circulating markers of endothelial dysfunction: vWF 150.0 g/L (121.0-195.0) vs. 91.5 g/L (70.5-104.0), P < or = 0.0001, P-selectin 39.5 pg/L (34.0-40.6) vs. 34.8 pg/L (32.5-38.6) P=0.009. In contrast, levels of VCAM-1 were comparable between the groups. The levels of some inflammatory markers were related to the concentration of von Willebrand factor and P-selectin - IL-6: vWF (r=0.36, P=0.08), hs CRP: P-selectin (r=0.44, P=0.018), IL-6: P-selectin (r=0.51, P=0.0002), IL-8: P-selectin (r=0.38, P=0.043).. Patients with idiopathic venous thrombosis have increased levels of circulating markers of inflammation and blood markers of endothelial dysfunction. Higher levels of both groups of markers indicate that patients in the stable phase of the disease have an increased systemic inflammatory response. The interrelationship between inflammatory markers and markers of endothelial dysfunction favour the hypothesis that inflammation could be involved in the etiopathogenesis of idiopathic venous thrombosis.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Endothelium, Vascular; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Lower Extremity; Male; Middle Aged; P-Selectin; Tumor Necrosis Factor-alpha; Up-Regulation; Vascular Cell Adhesion Molecule-1; Venous Thrombosis; von Willebrand Factor

Interleukin-8 (IL-8) has been shown previously to associate with different individual clinical manifestations and activity of Behcet's disease (BD), but its association with vascular involvement has not been established.. Forty-five untreated patients with BD and 29 healthy individuals were included in the study. The activity of patients was based on the existence of two or more symptoms and a statistically significantly high Behcet's Disease Activity Index (BDAI) at the time of the study. IL-8, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) results were evaluated with respect to activity, vascular involvement, and other specific individual clinical manifestations of the disease.. IL-8 levels were found to be significantly elevated in active BD compared with inactive BD (P = 0.006) and healthy controls (P = 0.000), with median values of 267 (53-2000), 137 (52-290), and 58 pg/mL (53-160 pg/mL), respectively. Unlike ESR and CRP, IL-8 levels showed a high correlation with BDAI scores (r = 0.743, P = 0.00) and the number of active clinical manifestations (r = 0.646, P = 0.00). Serum levels of IL-8 were increased in patients with oral ulcers, genital ulcers, eye lesions, and vascular lesions, with median values and significance levels of 254.5 (53-2000), P = 0.05; 254.5 (52-1400), P = 0.03; 254.5 (72-2000), P = 0.029; and 593 pg/mL (110-2000 pg/mL), P = 0.001, respectively. In addition, IL-8 levels in the active patient group with vascular involvement were significantly higher than the levels in those without vascular involvement.. Serum IL-8 levels are increased in the active phase of BD. This marker may be useful in the early detection of vascular involvement.

Topics: Adult; Behcet Syndrome; Biomarkers; Blood Sedimentation; C-Reactive Protein; Female; Humans; Interleukin-8; Male; Vasculitis; Venous Thrombosis

Deep venous thrombosis (DVT) resolution involves fibrinolysis, neovascularization, and fibrosis. We hypothesized that promoting neovascularization would accelerate DVT resolution.. A rat model of stasis DVT was produced with proximal ligation of the inferior vena cava (IVC) and all visible tributaries. One microg of interferon inducible protein (IP-10; angiostatic chemokine), basic fibroblast growth factor (bFGF; pro-angiogenic cytokine), epithelial neutrophil activating protein (ENA-78; pro-angiogenic chemokine), or saline solution control was injected into the IVC after ligation, and then via tail vein injection daily until sacrifice at either 4 or 8 days. Peripheral blood counts were measured, and thrombus weight was recorded at sacrifice. Laser Doppler in vivo imaging was used to estimate post-thrombotic IVC blood flow. Immunohistologic assessment of the thrombosed IVC for polymorphonuclear neutrophils (PMNs), monocytes (ED-1), and laminin (neovascular channels) was performed or the thrombus was separated from the IVC and assayed for keratinocyte cytokine (KC), monocyte chemotactic protein-1 (MCP-1), bFGF with enzyme-linked immunosorbent assay (ELISA), and total collagen with a direct colorimetric assay.. Peripheral blood and intrathrombus PMNs and monocytes were not significantly different in the treated or control rats. There were no differences in any measure at 4 days. At 8 days, thrombus neovascularity, but not weight or collagen content, was increased in rats treated with bFGF or ENA-78 compared with control rats (17.6 +/- 0.93, 16.2 +/- 0.97 vs 13.2 +/- 0.79; channels/5 high-power fields (hpf; n = 6-10; P <.05). Post DVT IVC blood flow was significantly increased in bFGF-treated rats but not in rats treated with IP-10 or ENA-78, as compared with control rats. Rats treated with ENA-78 had increased intrathrombus bFGF compared with control rats (85 +/- 27 pg/mg protein vs 20 +/- 6 pg/mg protein; n = 6; P <.05), but other mediators were not significantly different in treated rats compared with control rats.. Pro-angiogenic compounds increase thrombus neovascularization, but this does not correlate with smaller or less fibrotic DVT. Mechanisms other than neovascularization may be more important to hasten DVT dissolution. Clinical relevance Improved therapy for deep venous thrombosis (DVT) will ideally increase the rate of thrombus dissolution and eliminate the bleeding risks of anticoagulation. This study evaluated promoting DVT neovascularization with angiogenic chemokines, and, while successful by experimental measures, this did not translate into smaller DVT. Solely promoting thrombus neovascularization will not likely speed resolution.

Topics: Animals; Chemokine CXCL10; Chemokine CXCL5; Chemokines, CXC; Disease Models, Animal; Fibroblast Growth Factor 2; Interleukin-8; Male; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Ultrasonography; Vena Cava, Inferior; Venous Thrombosis

Elevated plasma levels of interleukin 8 (IL-8) were previously shown to be associated with recurrent venous thrombosis. To assess the risk of venous thrombosis, IL-8 plasma concentrations were measured in patients and control subjects of the Leiden Thrombophilia Study (LETS). This population based case-control study included 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched controls. The risk of venous thrombosis for subjects with elevated IL-8 levels (above 90th percentile of controls) compared with subjects with IL-8 levels below the 90th percentile was increased 1.8-fold (95%CI 1.2-2.8). Adjusted for age and sex, the odds ratio was 1.9 (95%CI 1.3-2.8). IL-8 concentrations were weakly correlated with age, male sex, and concentrations of C-reactive protein, factor VIII coagulation activity and homocysteine, but adjustment for these factors did not substantially affect the association between IL-8 and venous thrombosis. Our results suggest that IL-8 is a risk factor for venous thrombosis.

Topics: Adolescent; Adult; Age Factors; Aged; Anticoagulants; C-Reactive Protein; Case-Control Studies; Factor VIII; Female; Homocysteine; Humans; Interleukin-8; Male; Middle Aged; Odds Ratio; Risk; Risk Factors; Sex Factors; Venous Thrombosis

Inflammatory mediators are involved in activation of the coagulation system, and elevated plasma concentrations of IL-6 and IL-8 are associated with an increased risk of venous thrombosis. Using serologic and molecular biologic tests, we investigated in a case-control study on patients with recurrent venous thrombosis the association between Chlamydia (C) pneumoniae and venous thrombosis and we evaluated the relation between C. pneumoniae serology and the cytokines IL-6 and IL-8. The presence of C. pneumoniae antibody titers > or = 1:16 was not associated with an increased risk of venous thrombosis (odds ratio 0.8 95% CI, 0.4-1.7). Circulating C. pneumoniae-DNA was detected in only one patient and two control subjects. IgG antibody titers against C. pneumoniae were not correlated with the concentrations of IL-6 and IL-8. These results indicate that the inflammatory process shown in patients with venous thrombosis is not related to C. pneumoniae.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Case-Control Studies; Chlamydia Infections; Chlamydophila pneumoniae; Female; Humans; Immunoglobulin G; Immunologic Tests; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Seroepidemiologic Studies; Venous Thrombosis

Deep vein thrombosis (DVT) is a multifactorial disease. Recently, inflammation has been suggested as a risk factor for DVT. The question is whether inflammation is a cause of venous thrombosis or rather a result of the thrombotic process.. We studied the inflammatory response in the acute phase of DVT with interleukin-6, interleukin-8, and C-reactive protein (CRP) as inflammatory markers. Plasma concentrations were measured on the day of admission (day 0) in 40 patients with acute DVT confirmed with phlebography and in 33 patients with clinical suspicion of DVT but negative phlebography results (controls). In patients with DVT, inflammatory markers were also examined on five subsequent days.. On day 0, the median concentrations in plasma of interleukin-6, interleukin-8, and CRP were 15.0 pg/mL (range, <3 to 70 pg/mL), 7.0 pg/mL (range, <3 to 76 pg/mL), 37.5 mg/L (range, <7 to 164 mg/L), respectively, in the patient group and less than 3 pg/mL (range, <3 to 11 pg/mL; P <.001), 6.0 pg/mL (range, <3 to 52 pg/mL; P =.08), and 5.0 pg/L (range, <7 to 66 pg/L; P <.001), respectively, in the controls. During the next days, interleukin-6 concentration showed a gradual decline in patients with DVT from 15.0 to 5.5 pg/mL (P <.001), interleukin-8 concentration was relatively constant in time, and CRP concentration declined from 37.5 to 21.5 mg/L (P =.01).. Our data show an apparent inflammatory response with highest measured concentrations of inflammatory markers on the day of admission and a subsequent decrease during the next days. This response supports the hypothesis that elevated inflammatory markers are a result rather than a cause of venous thrombosis.

Topics: Acute-Phase Reaction; C-Reactive Protein; Case-Control Studies; Female; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Phlebography; Risk Factors; Venous Thrombosis

Therapy for deep vein thrombosis (DVT) resolution in those patients in whom a complication or contraindication to anticoagulation occurs is limited. As prior work suggests that thrombus maturation involves early influx of neutrophils (PMN) and neovascularization, we hypothesized that administering the proinflammatory/proangiogenic chemokine interleukin (IL)-8 might accelerate thrombus resolution.. An established rodent model of DVT (inferior vena cava [IVC] ligation) was used whereby daily intravenous recombinant human IL-8 (1 microg) or vehicle control was administered, with sacrifice at 4 and 8 days. Prior to sacrifice and at harvest, duplex ultrasound of the DVT and femoral venous pressure measurements were performed. Thrombi were analyzed by immunohistochemical techniques for PMN, monocytes, and neovascularization; for chemokines, by enzyme-linked immunoassay; and fibrosis, by hydroxyproline assay and trichrome staining.. IL-8 accelerated thrombus dissolution 4 days after IVC ligation, with 6-fold increased thrombus blood flow by duplex ultrasound and a 23% increased absolute femoral venous pressure compared with controls (both P < 0.05). These findings may be partially explained by the fact that animals receiving IL-8, as compared with controls, had 2.5-fold greater thrombus neovascularization (with a trend continuing to 8 days) and increased PMN at 4 days. Thrombus vascular endothelial growth factor was significantly reduced at 8 days postligation, while monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha were not altered by IL-8 administration. At 8 days post-IVC-ligation, fibrosis was 12-fold greater with IL-8 treatment compared with controls.. A proinflammatory/proangiogenic thrombus milieu, as conferred by IL-8, enhances thrombus resolution and underscores the important relationship between neovascularity and inflammation.

Topics: Animals; Chemokines; Endothelial Growth Factors; Fibrosis; Hypertension; Interleukin-8; Leukocyte Count; Lymphokines; Male; Neovascularization, Physiologic; Neutrophils; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Venous Pressure; Venous Thrombosis

Topics: Adenocarcinoma; Autoantibodies; Humans; Interleukin-8; Male; Middle Aged; Paraneoplastic Syndromes; Pleural Neoplasms; Venous Thrombosis

Inflammatory processes may play a key role in venous thrombosis, by inducing a procoagulant state through the action of cytokines and chemokines on monocytes and endothelial cells. Plasma concentrations of three inflammatory mediators, interleukin 6 (IL-6), interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1), that mediate the cross-talk between inflammation and coagulation, were measured in 182 subjects with recurrent venous thrombosis and 350 healthy subjects recruited through a general practice. Elevated levels of IL-6 (>90th percentile of the control group) were detected in 25.8% of the patients with venous thrombosis in comparison with 10% (by definition) of the controls [odds ratio 2.4 (95%CI 1.5-3.8)]. In 21.5% of the patients elevated plasma levels of IL-8 (>90th percentile) were determined [odds ratio 2.0 (95%CI 1.2-3.5)]. Elevated levels of MCP-1 (>90th percentile) were detected in 24.1% of the patients [odds ratio 1.9 (95%CI 1.2-3.2)]. This is the first large clinical study showing that an increase in inflammatory mediators is associated with venous thrombosis. Future prospective studies are necessary to clarify the causal nature of the inflammatory process with respect to venous thrombosis.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chemokine CCL2; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Netherlands; Odds Ratio; Recurrence; Thrombophlebitis; Venous Thrombosis

Thrombus organization after venous thromboembolism leading to recanalization occurs at a variable rate. The angiogenic chemokine interleukin-8 (IL-8) has been found in thrombus months after thrombus initiation. We hypothesize that thrombus organization involves neovascularization and leukocyte influx and that IL-8 administered at thrombus induction will promote thrombus organization.. A group of rats underwent inferior vena caval occlusive thrombosis. At thrombus induction and every 24 hours, the rats were administered IL-8 (1 microgram) or serum albumin. The rats were killed at either day 4, day 8, or day 12, and, at death, colloidal carbon was perfused via the heart. The inferior vena cava was isolated, measured, weighed, and formalin fixed. The sections were stained with anti-polymorphonuclear leukocyte antibody, the endothelial marker factor VIII-related antigen, and with hematoxylin and eosin. Thrombus neovascularization (colloidal carbon) with morphometric analysis was normalized to the total thrombus area. In addition, the rats underwent perfusion with fluorescein isothiocyanate dextran (molecular weight, 150,000) at death to correlate with colloidal carbon perfusion, and thrombus fluorescence was determined.. Thrombus cellularity initially involved neutrophils, followed by monocytes. Significantly more neutrophils, monocytes, and cells that were defined as spindle shaped (fibroblasts and endothelial cells) were noted in the animals treated with IL-8. Neovascularization was significantly increased at day 4 in the animals treated with IL-8 versus the animals treated with serum albumin and was corroborated with a significant increase in thrombus fluorescein isothiocyanate dextran fluorescence at day 4 in the rats treated with IL-8. Colloidal carbon perfusion was noted within vascular channels without extravasation and colocalized with factor VIII-related antigen.. This study shows that thrombus organization involves neovascularization and that IL-8 augments thrombus organization.

Topics: Animals; Carbon; Drug Combinations; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Interleukin-8; Microscopy, Fluorescence; Neovascularization, Pathologic; Povidone; Rats; Serum Albumin; Vena Cava, Inferior; Venous Thrombosis