Interleukin-6 and d-dimer levels are associated with vascular dysfunction in patients with untreated HIV infection

Abstract Persistent viral activity may cause enduring seropositivity and inflammation in treated people with HIV (PWH). We compared inflammatory biomarkers between early treated PWH who remained seronegative or seroconverted and found similar levels of D-dimer, soluble cluster of differentiation 14, C-reactive protein, and interleukin-6, indicating that seronegativity does not affect chronic inflammation in early treated PWH.

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Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiw173 ◽

2016 ◽

Vol 214 (3) ◽

pp. 408-416 ◽

Cited By ~ 40

Author(s):

Álvaro H. Borges ◽

Jemma L. O'Connor ◽

Andrew N. Phillips ◽

James D. Neaton ◽

Birgit Grund ◽

...

Keyword(s):

Hiv Infection ◽

Interleukin 6 ◽

High Sensitivity ◽

C Reactive Protein ◽

Reactive Protein ◽

Clinical Events ◽

D Dimer

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Biomarker Profiling of Neurovascular Diseases in Patients with Stage 5 Chronic Kidney Disease

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618807565 ◽

2018 ◽

Vol 24 (9_suppl) ◽

pp. 248S-254S

Author(s):

Justin Lee ◽

Jack Bontekoe ◽

Brandon Trac ◽

Vinod Bansal ◽

José Biller ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Carotid Artery Disease ◽

Vascular Dysfunction ◽

Enzyme Linked Immunosorbent Assay ◽

Neurocognitive Deficits ◽

Intracranial Atherosclerotic Disease ◽

Artery Disease ◽

D Dimer ◽

Neurovascular Diseases

Patients with stage 5 chronic kidney disease (CKD5D) have a higher risk of developing neurocognitive deficits. Stroke, cervical carotid artery disease (CCAD), and intracranial atherosclerotic disease (ICAD) are causes of such deficits in CKD5D. Chronic inflammation from renal failure elevates risk for these diseases through oxidative stress and vascular dysfunction. The adverse impact on the carotid and intracranial vasculatures contributes to the multifactorial pathophysiology of stroke. Eleven plasma biomarker levels in patients with CKD5D (n = 97) and healthy controls (n = 17-50) were measured using sandwich enzyme-linked immunosorbent assay (ELISA) method. Of the 97 patients with CKD5D, 24 had CCAD, 19 had ICAD, and 23 had acute stroke. Elevations in NACHT, LRR, and PYD domains-containing protein 3 (NALP3) levels in patients with CKD5D (+)CCAD (1.80 ± 0.11 ng/mL) compared to patients with (−)CCAD (1.55 ± 0.08 ng/mL) were statistically significant ( P = .0299). Differences in D-dimer levels were also found to be statistically significant ( P = .0258) between CKD5D (+)stroke (1.83 ± 0.42 μg/mL) and (−)stroke (0.89 ± 0.13 μg/mL) groups. The ages of the (+) neurovascular disease groups were found to be significantly elevated compared to the (−) neurovascular disease groups ( P = .0002 carotid AD; P < .0001 ICAD; P = .0157 stroke). D-dimer levels were positively correlated with age in CKD5D ( P = .0375). With the possible exception of NALP3 for CCAD, profiling levels of specific biomarkers for risk stratification of neurovascular diseases in the CKD5D population warrants further investigation.

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Vitamin C blocks vascular dysfunction and release of interleukin-6 induced by endothelin-1 in humans in vivo

Atherosclerosis ◽

10.1016/j.atherosclerosis.2006.02.018 ◽

2007 ◽

Vol 190 (2) ◽

pp. 408-415 ◽

Cited By ~ 34

Author(s):

Felix Böhm ◽

Magnus Settergren ◽

John Pernow

Keyword(s):

Vitamin C ◽

Interleukin 6 ◽

Vascular Dysfunction ◽

Endothelin 1

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Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation

Blood ◽

10.1182/blood-2009-03-210179 ◽

2010 ◽

Vol 115 (2) ◽

pp. 161-167 ◽

Cited By ~ 166

Author(s):

Nicholas T. Funderburg ◽

Elizabeth Mayne ◽

Scott F. Sieg ◽

Robert Asaad ◽

Wei Jiang ◽

...

Keyword(s):

Hiv Infection ◽

Tissue Factor ◽

Immune Activation ◽

Interleukin 6 ◽

Plasma Levels ◽

Thrombus Formation ◽

Hiv Replication ◽

Increased Risk

Abstract HIV infection is associated with an increased risk of thrombosis; and as antiretroviral therapy has increased the lifespan of HIV-infected patients, their risk for cardiovascular events is expected to increase. A large clinical study found recently that all-cause mortality for HIV+ patients was related to plasma levels of interleukin-6 and to D-dimer products of fibrinolysis. We provide evidence that this elevated risk for coagulation may be related to increased proportions of monocytes expressing cell surface tissue factor (TF, thromboplastin) in persons with HIV infection. Monocyte TF expression could be induced in vitro by lipopolysaccharide and flagellin, but not by interleukin-6. Monocyte expression of TF was correlated with HIV levels in plasma, with indices of immune activation, and with plasma levels of soluble CD14, a marker of in vivo lipopolysaccharide exposure. TF levels also correlated with plasma levels of D-dimers, reflective of in vivo clot formation and fibrinolysis. Thus, drivers of immune activation in HIV disease, such as HIV replication, and potentially, microbial translocation, may activate clotting cascades and contribute to thrombus formation and cardiovascular morbidities in HIV infection.

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Independent Association of Interleukin 6 With Low Dynamic Lung Function and Airflow Limitation in Well-Treated People With Human Immunodeficiency Virus

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa600 ◽

2020 ◽

Author(s):

Rebekka F Thudium ◽

Andreas D Knudsen ◽

Jakob Hjorth Von Stemann ◽

Malene Hove-Skovsgaard ◽

Hedda Hoel ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Lung Function ◽

Hiv Infection ◽

Interleukin 6 ◽

Smoking Status ◽

Airflow Limitation ◽

Pulmonary Diseases ◽

Increased Risk ◽

Immunodeficiency Virus ◽

Chronic Pulmonary Diseases

Abstract Background Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH. Methods We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices. Results PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (−212 mL [95% confidence interval, −308 to −116 mL]), lower forced vital capacity (−208 mL [−322 to −93 mL]), and airflow limitation (aOR, 2.62 [1.58–4.36]) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005). Conclusion IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.

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Practical Management of Castleman's Disease

Acta Haematologica ◽

10.1159/000444515 ◽

2016 ◽

Vol 136 (1) ◽

pp. 16-22

Author(s):

Musa Fares Alzahrani ◽

Mansoor Radwi ◽

Heather A. Leitch

Keyword(s):

Hiv Infection ◽

Interleukin 6 ◽

Lymphoproliferative Disorder ◽

Treatment Options ◽

Castleman’S Disease ◽

Human Herpesvirus ◽

Human Herpesvirus 8 ◽

Castleman's Disease ◽

Herpesvirus 8 ◽

Hiv Negative

Castleman's disease (CD) is a rare lymphoproliferative disorder that is most commonly present in multicentric (MCD) form in association with HIV infection. Interleukin-6 (IL-6) and human herpesvirus-8 (HHV-8) play major roles in MCD pathogenesis. Important treatment options have recently become available, particularly with the introduction of IL-6 and IL-6 receptor inhibitors for the treatment of HIV-negative patients with MCD. Though advances in therapy may improve outcomes in some patients, the prognosis remains guarded, and a stratified approach to the management of MCD is needed.

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Interleukin-6, Fibrin D-Dimer, and Coagulation Factors VII and XIIa in Prediction of Coronary Heart Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/01.atv.0000135995.39488.6c ◽

2004 ◽

Vol 24 (8) ◽

pp. 1529-1534 ◽

Cited By ~ 90

Author(s):

Gordon D.O. Lowe ◽

Ann Rumley ◽

Alex D. McMahon ◽

Ian Ford ◽

Denis St. J. O’Reilly ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Interleukin 6 ◽

Coagulation Factors ◽

D Dimer

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Reduced P53 Protein Level and Evidence of Ongoing Coagulation among HIV-Infected Persons Accessing Treatment at University of Calabar Teaching Hospital, Nigeria

Journal of Cancer and Tumor International ◽

10.9734/jcti/2019/v9i330111 ◽

2019 ◽

pp. 1-6

Author(s):

E. C. Akwiwu ◽

A. O. Okafor ◽

J. O. Akpotuzor ◽

E. E. Onukak

Keyword(s):

Hiv Infection ◽

Teaching Hospital ◽

P53 Protein ◽

Distribution Width ◽

Cd4 Cell Count ◽

Persons Living With Hiv ◽

The University ◽

Living With Hiv ◽

Cd4 Cell ◽

D Dimer

Aims: To assess tumour suppressing activity and ongoing coagulation among persons living with HIV infection and accessing care in the University of Calabar Teaching Hospital, Nigeria. Study Design: Case-control study. Place and Duration of Study: University of Calabar Teaching Hospital Calabar, Nigeria, between April 2018 and November 2018. Methods: Ninety persons living with HIV infection who were attending clinics at the University of Calabar Teaching Hospital were enrolled with ninety age and sex-matched HIV seronegative individuals who served as control subjects. The blood specimen was collected from each participant for analyses of CD4 cell and full blood counts by automation, serum was used for the assays of P53 protein and D-dimer levels using enzyme-linked immunosorbent assay test kits. Data analysis was done using SPSS version 22.0. Student t-test was used to compare means between test and control subjects. One-way analysis of variance was used to compare means across the HAART-naïve and two other groups on different HAART protocols. Statistical significance was drawn at a p≤ 0.05. Results: The CD4 cell count and P53 protein level reduced while D-dimer level increased in HIV infection. Platelet count also reduced while platelet distribution width increased with the condition. While CD4 cell count improved with Highly Active Antiretroviral Therapy administration, D-dimer level, mean platelet volume and platelet distribution width reduced. Conclusion: This study observed reduced tumour suppression and increased coagulation activities alongside immunosuppression in HIV infection.

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A Data Analysis of D-Dimer & Interleukin-6 (IL-6) Test for Covid Patient

Austin Journal of Infectious Diseases ◽

10.26420/austinjinfectdis.2021.1052 ◽

2021 ◽

Vol 8 (3) ◽

Author(s):

Batabyal B ◽

◽

Roy P ◽

Das A ◽

◽

...

Keyword(s):

Immune Response ◽

Data Analysis ◽

Interleukin 6 ◽

Inflammatory Cytokine ◽

Laboratory Data ◽

Factor Xiiia ◽

Thrombosis Prophylaxis ◽

Soluble Fibrin ◽

D Dimer

Various biomarkers, especially inflammatory markers like C-reactive protein (CRP), ferritin, fibrinogen, D-dimer and Interleukin 6 (IL-6) are associated with Covid-19 progression. Thrombosis prophylaxis with low molecular weight heparin has shown beneficial results in preventing coagulopathy a reducing risk of mortality due to thrombotic events. The COVID-19 patients highlighting the role of D-dimer, and Interleukin-6 (IL-6). During plasma coagulation soluble fibrin is generated by the influence of thrombin on fibrinogen. The soluble fibrin is crosslinked to the vessel walls by factor XIIIa. When splitting this cross linked fibrin, characteristic products called D-dimers are released. Increased D-dimer concentrations are found in thrombotic diseases and microthrombotic events (e.g. in case of disseminated intravascular coagulation, DIC). D-dimer determination is mainly used to exclude deep vein thrombosis of the leg and pulmonary embolism. D-Dimer levels rise during pregnancy and high levels are associated with complications. D-dimer is a fibrin degradation product that is often used to measure and assess clot formation. Amid the COVID-19 pandemic, elevated D-dimer levels have been associated with disease severity and mortality trends. Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. IL-6 is also secreted by macrophages in response to specific microbial molecules, referred to as Pathogen Associated Molecular Patterns (PAMPs), which trigger the innate immune response and initiate inflammatory cytokine production. IL-6 is one of the most important mediators of fever and of the acute phase response. IL-6 is also called a “myokine”, a cytokine produced from muscle that increases in response to muscle contraction. Additionally, osteoblasts secrete IL-6 to stimulate osteoclast formation. The detection and control of pro-inflammatory response is crucial in the early stages of viral infection. COVID-19 is an emerging viral disease of global concern and optimal treatment has yet to be determined. Unknown response of treatment of COVID-19 is important during patient monitoring. IL-6 is one of the key cytokines after activated macrophages. Here we will present a laboratory data analysis of COVID-19 patients in different age group highlighting the role of positivity D-dimer and interleukin-6 (IL-6).

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