Nonclinical Characterization of Bexmarilimab, a Clever-1-Targeting Antibody for Supporting Immune Defense Against Cancers.

Common lymphatic endothelial and vascular endothelial receptor-1 (Clever-1) is a multifunctional type-1 transmembrane protein that plays an important role in immunosuppression against tumors. Clever-1 is highly expressed in a subset of human tumor-associated macrophages and associated with poor survival. In mice, Clever-1 supports tumor growth and metastasis formation, and its deficiency or blockage induces T-cell-dependent killing of cancer cells.

Novel Biomarkers for Diagnosing Periprosthetic Joint Infection from Synovial Fluid and Serum.

Background: Synovial fluid bacterial culture is the cornerstone of confirmation or exclusion of periprosthetic joint infection (PJI). The aim of this study was to assess synovial fluid and serum biomarker patterns of patients with total joint arthroplasty (TJA), and the association of these patterns with PJI.

Methods: Synovial fluid and serum samples were collected from 35 patients who were admitted to the Arthroplasty Unit of the Department of Orthopaedics and Traumatology at Turku University Hospital.

The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease.

Objective: This study aimed to investigate the role of cytokines as intermediates in the pathway from increased adiposity to disease.

Methods: BMI and circulating levels of up to 41 cytokines were measured in individuals from three Finnish cohort studies (n = 8,293). Mendelian randomization (MR) was used to assess the impact of BMI on circulating cytokines and the impact of BMI-driven cytokines on risk of obesity-related diseases.

Effect of Intravenous Interferon β-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

Importance: Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage.

Objective: To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS.

The influence of dexmedetomidine and propofol on circulating cytokine levels in healthy subjects.

Background: Surgery and diseases modify inflammatory responses and the immune system. Anesthetic agents also have effects on the human immune system but the responses they induce may be altered or masked by the surgical procedures or underlying illnesses. The aim of this study was to assess how single-drug dexmedetomidine and propofol anesthesia without any surgical intervention alter acute immunological biomarkers in healthy subjects.

Maternal tiredness and cytokine concentrations in mid-pregnancy.

Objective: Sleep disturbances relate to altered levels of inflammatory mediators in general population, but not much is known about the associations between sleep disturbances and inflammatory mediators during pregnancy. The present exploratory study investigated whether insomnia, tiredness, general sleep quality, and insufficient sleep duration during pregnancy relate to the concentrations of maternal peripheral circulating cytokines. As sleep disturbances are frequently observed in mood disorders, the results were controlled for symptoms of depression and anxiety.

Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy.

Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines.

Serum cytokine levels differ according to major cardiovascular risk factors in patients with lower limb atherosclerosis.

Different cardiovascular risk factors present a heterogenic manifestation of lower limb atherosclerosis. The molecular mechanisms behind this phenomenon remain unknown. We aimed to clarify this phenomenon by studying the association of major cardiovascular risk factors with the profile of serum cytokines in 226 consecutive patients with lower limb atherosclerosis treated at a department of Vascular Surgery during a one-year enrollment period.

Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease.

Introduction: The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades.

Methods: The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment.

Comparison of the efficacy and safety of FP-1201-lyo (intravenously administered recombinant human interferon beta-1a) and placebo in the treatment of patients with moderate or severe acute respiratory distress syndrome: study protocol for a randomized controlled trial.

Background: Acute respiratory distress syndrome (ARDS) results in vascular leakage, inflammation and respiratory failure. There are currently no approved pharmacological treatments for ARDS and standard of care involves treatment of the underlying cause, and supportive care. The vascular leakage may be related to reduced concentrations of local adenosine, which is involved in maintaining endothelial barrier function.

Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors.

Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) of up to 8,293 Finns we identified 27 genome-widely significant loci (p < 1.2 × 10) for one or more cytokines.

Cerebrospinal fluid cytokines in Lyme neuroborreliosis.

Background: Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies.

Soluble CD73 in Critically Ill Septic Patients - Data from the Prospective FINNAKI Study.

Background: CD73 dephosphorylates adenosine monophosphate to adenosine that is an anti-inflammatory molecule inhibiting immune activation and vascular leakage. Therefore, CD73 could be an interesting mediator both in sepsis and acute kidney injury (AKI). We aimed to explore the soluble CD73 (sCD73) levels and their evolution in critically ill patients with severe sepsis and, second, to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality.

Cytokine profile and maternal depression and anxiety symptoms in mid-pregnancy-the FinnBrain Birth Cohort Study.

Maternal prenatal psychological symptoms are associated with child health outcomes, e.g., atopic diseases.

Compared to Intermittant Claudication Critical Limb Ischemia Is Associated with Elevated Levels of Cytokines.

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease (PAD) and associated with an extremely poor clinical outcome. In order to understand the possible role of circulating cytokines and poor outcome associated with CLI we compared the circulating cytokine profile of patients with CLI against patients with intermittent claudication (IC). The levels of 48 circulating cytokines were examined in 226 consecutive patients with peripheral artery disease (PAD) admitted for elective, non-urgent, invasive treatment of IC or CLI.

Circulating Cytokines Predict the Development of Insulin Resistance in a Prospective Finnish Population Cohort.

Context: Metabolic inflammation contributes to the development of insulin resistance (IR), but the roles of different inflammatory and other cytokines in this process remain unclear.

Objective: We aimed at analyzing the value of different cytokines in predicting future IR.

Design, Setting, And Participants: We measured the serum concentrations of 48 cytokines from a nationwide cohort of 2200 Finns (the Cardiovascular Risk in Young Finns Study), and analyzed their role as independent risk factors for predicting the development of IR 4 years later.

G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer.

Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and a strong infiltration by TAMs has been associated with estrogen receptor (ER)-negative tumors and poor prognosis. However, the molecular mechanisms behind these observations are unclear. We investigated macrophage activation in response to co-culture with several breast cancer cell lines (T47D, MCF-7, BT-474, SKBR-3, Cal-51 and MDA-MB-231) and found that high granulocyte colony-stimulating factor (G-CSF) secretion by the triple-negative breast cancer (TNBC) cell line MDA-MB-231 gave rise to immunosuppressive HLA-DR macrophages that promoted migration of breast cancer cells via secretion of TGF-α.

The Biomarker GlycA Is Associated with Chronic Inflammation and Predicts Long-Term Risk of Severe Infection.

The biomarker glycoprotein acetylation (GlycA) has been shown to predict risk of cardiovascular disease and all-cause mortality. Here, we characterize biological processes associated with GlycA by leveraging population-based omics data and health records from >10,000 individuals. Our analyses show that GlycA levels are chronic within individuals for up to a decade.

Hypoxia-induced inflammation and purinergic signaling in cross clamping the human aorta.

Open aortic surgery evokes a systemic inflammatory response and is associated with high morbidity and mortality. Purinergic signaling has been shown to be crucial for maintaining vascular integrity and attenuating inflammation related to hypoxia. The involvement of purinergic signaling in cross clamping of major human arteries is unknown.

Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate.

Escherichia coli amine oxidase (ECAO), encoded by the tynA gene, catalyzes the oxidative deamination of aromatic amines into aldehydes through a well-established mechanism, but its exact biological role is unknown. We investigated the role of ECAO by screening environmental and human isolates for tynA and characterizing a tynA-deletion strain using microarray analysis and biochemical studies. The presence of tynA did not correlate with pathogenicity.

Consequences of the lack of CD73 and prostatic acid phosphatase in the lymphoid organs.

CD73, ecto-5'-nucleotidase, is the key enzyme catalyzing the conversion of extracellular AMP to adenosine that controls vascular permeability and immunosuppression. Also prostatic acid phosphatase (PAP) possesses ecto-5'-nucleotidase/AMPase activity and is present in leukocytes. However, its role related to immune system is unknown.

Postnatal development and LPS responsiveness of pulmonary adenosine receptor expression and of adenosine-metabolizing enzymes in mice.

Background: Adenosine levels are regulated by ecto-5'-nucleotidase/CD73 and adenosine deaminase (ADA). Adenosine regulates endothelial permeability and anti-inflammatory responses via adenosine receptors. Here, the adenosine receptors and purine-converting enzymes were studied during postnatal development and inflammation.

Early prediction of persistent organ failure by soluble CD73 in patients with acute pancreatitis*.

Objective: New biomarkers are needed to better predict the severity of acute pancreatitis. CD73/ecto-5'-nucleotidase is an enzyme that generates adenosine, which dampens inflammation and improves vascular barrier function in several disease models. CD73 also circulates in a soluble form in the blood.

Distribution and medical impact of loss-of-function variants in the Finnish founder population.

Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.