Serum Levels Of Cytokines In Patients Research Articles

Markers of chronic low-grade inflammation and serum cytokine levels in patients with type 1 diabetes: associations with time in ranges and glucose variability

BACKGROUND: Increased glucose variability is recognized as a risk factor for vascular diabetic complications. It is assumed that deteriorating effect of GV on blood vessels can be realized through the activation of inflammatory signaling pathways.AIM: to determine associations of low-grade inflammation markers and serum cytokines with time in ranges and GV parameters derived from continuous glucose monitoring (CGM) in patients with type 1 diabetes (T1D).MATERIALS AND METHODS: In 470 adult patients with T1D, high-sensitivity C-reactive protein (hsCRP) and fibrinogen was measured, neutrophil-lymphocyte ratio (NLR) and the Systemic Immune-inflammation Index (SII) were calculated. In a sample of 130 patients and 20 healthy individuals (control), serum concentrations of interleukins (IL-1β, IL-4, IL-6, sIL-6Rα, IL-19, IL-20, IL-22, IL-26, IL-27, IL-28A, IL-29, IL-32, IL-34, IL-35) were assessed by multiplex analysis. Time in the ranges and GV parameters: Coefficient of Variability (CV), Mean Amplitude of Glycemic Excursions (MAGE), and Mean Absolute Glucose rate of changes (MAG) were derived from CGM data.RESULTS: Patients with Time In Range (TIR) <70% had higher concentrations of hs-CRP and fibrinogen, higher SII values, and demonstrated a trend toward higher TIR compared with those with TIR ≥70% (p=0.018, p=0.026, p=0.037, p=0.101, respectively). Patients with T1D, when compared to control, demonstrated increased concentrations of IL-1β (p<0.0001), IL-6 (p<0.0001), decreased levels of IL-4 (p=0.002), and a tendency to decrease IL-22 and IL-29 (p=0.1). Patients with TIR>70% had higher levels of IL-4 (p=0.02) as well as lower concentrations of IL-1β (p=0.0003) and IL-6 (p=0.007) than patients with TIR≤70%. In a multivariate stepwise regression analysis including clinical data and CGM parameters as independent variables, body mass index was positive predictor of hsCRP and fibrinogen levels, TIR was negatively associated with IL-20 and IL-34, time above range was associated positively with IL-1β, MAGE showed positive association with SII, IL-26 and IL28A, while MAG was positively associated with IL-29.CONCLUSION: T1D patients with non-target TIR (<70%) have higher levels of low-intensity inflammatory markers and serum pro-inflammatory cytokines than patients with TIR>70%. Both hyperglycemia and increased GV are associated with intensity of low-grade inflammation in T1D.

Терапия рассеянного склероза препаратами первой линии: уровень цитокинов и влияние герпетической инфекции

The effects of the disease modifying drugs (DMDs) for multiple sclerosis (MS), interferon beta (IFNβ) and glatiramer acetate (GA), on the cytokine levels of individuals with MS are poorly understood. The effects of persistent herpesvirus infection (PHVI) on the cytokine production during treatment with DMDs for MS have not been identified. The role of cytokines and PHVI in the development of the treatment-related adverse events (AEs) has not been determined. The study was aimed to assess serum cytokine levels in patients with MS treated or not treated with DMDs for MS, and to determine the relationships between the cytokine levels, herpesvirus infection, and AEs. A total of 36 patients (12 males and 24 females, median age 38.50 (28.00; 48.50) years) with relapsing-remitting MS (criteria by McDonald, 2010) were examined. PHVI reactivation was observed in 18 individuals; in 10 of them it was associated with the history of the virus-associated exacerbation (VAE) of MS or VAE detected during assessment. A total of 30 patients were treated with DMDs for MS: 16 individuals with IFNβ, 14 individuals with GA. Systemic AEs were reported in 9 individuals. Serum levels of 15 cytokines were determined using the xMAP multiplex technique. Patients with MS showed a significant increase in the levels of IL10 (p < 0.01) and IL33 (p < 0.001) relative to donors when treated or not treated with DMDs for MS; the increase in IL31 levels was reported only in naïve patients (p < 0.05). At the same time, individuals with MS had low levels of IL1β, IL17F, IL22, IL25, IL23, and TNFα (p < 0.01). We revealed no differences in cytokine levels in the context of taking IFNβ or GA. Elevated IL10 levels were associated with PHVI reactivation (p < 0.01). We revealed significant correlations between high levels of IL31 and VAE (p < 0.01), IL33 and PHVI (p < 0.01). The IL1β levels were significantly higher in individuals with PHVI reactivation treated with DMDs for MS. There were no differences in cytokine levels associated with the presence or absence of systemic AEs. The latter predominated in individuals with PHVI reactivation and VAE. The cytokine levels of individuals with MS are affected by treatment with DMDs for MS and herpesvirus infections.

Diagnostic value and correlation analysis of serum cytokine levels in patients with multiple system atrophy

Diagnostic value and correlation analysis of serum cytokine levels in patients with multiple system atrophy

Differences in serum cytokine levels distinguish between clinically noninvasive lung adenocarcinoma and invasive lung adenocarcinoma: A cross-sectional study.

Lung cancer incidence and mortality remain high and are now the leading cause of cancer-related death. Lung adenocarcinoma (LUAD) is one of the main histological subtypes of lung cancer. Previous studies have shown the role of inflammation in the development of lung cancer, but the relationship between cytokines and LUAD is still unclear. To further differentiate and explore the association of cytokines with the risk of non-invasive and invasive LUAD, we studied and assessed serum cytokine levels in patients with two types of LUAD. A cohort study of 90 non-invasive LUAD and 90 invasive LUAD was retrospectively included, and the clinical characteristics were recorded in detail. The differences in the levels of 12 serum cytokines (IFN-α, IFN-γ, IL-10, IL-12P70, IL-17A, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, and TNF-α) between the two groups of patients with LUAD were analyzed and evaluated. And we evaluated the clinical value of cytokine differential diagnosis of invasive LUAD based on receiver operating characteristics (ROC) curves. The mean age of the patients was 56.6 years, and the proportions of males and females were 38.9% and 61.1%, respectively. IFN-α, IL-1β, IL-2, IL-6, TNF-α, IL-4, and IL-8 were significantly increased in patients with invasive LUAD compared with the non-invasive LUAD group. Further research found that smoking is an important factor, with changes in the four cytokines IL-1β, IL-6, IL-8, and TNF-α being significantly higher in the smoking group of patients with invasive LUAD. It can be seen from the area under the curve that IL-1β and IL-2 have a significant differential diagnosis. We observed differences in preoperative serum cytokine levels between patients with invasive and non-invasive LUAD, which may serve as potential serum biomarkers for clinical differential diagnosis and disease progression assessment.

Cytokine profile in patients with obstructive coronary artery disease

Background. Studies of the role of cytokines in the pathogenesis of coronary artery disease (CAD) are quite relevant. Significant cytokine imbalance is mostly observed in patients with acute coronary syndrome. However, there are limited reports of serum cytokine levels in patients with chronic stable CAD. The problem of relationship between cytokines to the severity of coronary atherosclerosis is still urgent.Aim: To investigate the relationship between serum levels of cytokines and the severity of CAD.Material and Methods. Serum levels of IL-2, IL-4, IL-6, IL-10, TNF-a was analyzed in 24 healthy control patients and 70 patients with stable CAD who underwent coronary angiography. Coronary atherosclerosis was assessed with Gensini scoring system. Depending on the median of GS (38.0), the patients were divided into moderate CAD group (GS = 8–37) and severe CAD group (GS ≥ 38). The data were analyzed using Statistical Package for the Social Sciences (SPSS) software 26.0.Results. Patients with obstructive CAD presented higher TNF-α levels and lower IL-4. Patients with severe CAD increased IL-6 and reduced IL-2 levels. Logistic regression analysis showed that the IL-6 was independently related to the presence of obstructive CAD (OR = 3.836; 95% CI= 1.8–8.177). ROC analysis of the IL-6 logistic regression model showed that a cut-off of 5.19 pg/mL had 75.0 % sensitivity and 70.0 % specificity to predict severe atherosclerosis.Conclusion. Pro-inflammatory TNF-α and IL-6 cytokines increased, while regulatory IL-2 and anti-inflammatory IL-4 decreased in patients with stable CAD. Cytokine imbalance contributes to CAD progression. Elevated IL-6 levels and the pro-inflammatory potential of the blood increases in case of severe coronary atherosclerosis. It has been shown that with an increase in IL-6 levels, the odds of detecting severe CAD increases 3.5-folds.

The role of Th17 cells in chronic lymphocytic leukemia: friend orfoe?

T helper 17 (Th17) cells have a prominent role in autoimmune diseases. In contrast, the nature of these cells in cancer is controversial, with either pro- or antitumorigenic activities depending on various cancer settings. Chronic lymphocytic leukemia (CLL), a B-cell malignancy, is characterized by an imbalance in T-cell immune responses that contributes to disease progression and increased mortality. Many clinical reports indicate an increase in Th17 cells and/or interleukin 17 serum cytokine levels in patients with CLL compared with healthy individuals, which correlates with various prognostic markers and significant changes in the tumor microenvironment. The exact mechanisms by which Th17 cells might contribute to CLL progression remain poorly investigated. In this review, we provide an updated presentation of the clinical information related to the significance of Th17 cells in CLL and their interaction with the complex leukemic microenvironment, including various mediators, immune cells, and nonimmune cells. We also address the available data regarding the effects of CLL-targeted therapies on Th17 cells and the potential of using these cells in adoptive cell therapies. Having a sound understanding of the role played by Th17 cells in CLL is crucial for designing novel therapies that can achieve immune homeostasis and maximize clinical benefits.

Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID.

A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies.

Evaluation of Inflammatory Markers in Patients with Depressed Episodes in Major Depressive Disorder and Bipolar Disorder before and after Treatment.

Depression is one of the current dilemmas in both developed and developing societies. Studies show that the severity of psychiatric symptoms is directly related to the degree of inflammation caused by cytokines secreted by the immune system. Hence, evaluating serum cytokine levels in patients with depression can help to understand the pathogenesis of the disease and make the best therapeutic decisions. The present study investigated the levels of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in patients with major depression or bipolar disorder during depressive episodes (BDDE) before and after a 6-month pharmaceutical intervention. Patients referring to 3 clinics were recruited for the study. The diagnosis of major depression or bipolar disorder in a depressive phase was made according to the Diagnostic and Statistical Manual of Mental Disorders -5(DSM-5) criteria. There was a significant difference in depression levels between the pre-intervention and 6-month follow-up in both groups. After 6 months, IL-1 and IL-6 levels in the bipolar disorder group had decreased while TNF-α levels had increased. There was also a significant difference between pre-intervention and follow-up levels of IL-1. Serum levels of IL-1 and IL-6 decreased significantly in both groups after the 6-month follow-up, and symptom improvement was observed. TNF-α levels, on the other hand, decreased in the major depression group but increased in the bipolar disorder group. Considering that inflammation is a major outcome of depression, treatment strategies to reduce inflammation could be a practical approach to improving psychiatric symptoms.

Assessment of Serum Cytokine Levels in Patients with Hepatocellular Carcinoma and Those with Chronic Liver Disease: Cross-Sectional Study

Assessment of Serum Cytokine Levels in Patients with Hepatocellular Carcinoma and Those with Chronic Liver Disease: Cross-Sectional Study

Comparisons of lymphocytes profiles and inflammatory cytokines levels in blood of patients with differed severity of infection by human adenovirus type 7

BackgroundHuman adenovirus (HAdV) infection outbreak causes community-acquired pneumonia. Cellular immune dysfunction and hypercytokinemia play important roles in the pathogenesis of adenovirus respiratory infection. Some soluble factors in peripheral blood can assist in judging the virus-induced disease severity. The expression levels of inflammatory cytokines differ among patients with different disease severity. However, whether and how HAdV-7 infection influences the composition of blood immune cells and serum cytokine levels in patients at different disease stages, as well as the diagnosis values of these parameters, have rarely been intensively studied. We aimed to investigate lymphocytes profiles and cytokines levels in blood of patients at different disease stages upon human adenovirus type 7 (HAdV-7) infections, and explored the diagnosis values of the investigated parameters.MethodsPatients from two outbreaks of HAdV-7 in military of China were categorized into upper respiratory infection (URI) group, common pneumonia (CP) group and severe pneumonia (SP) group according to disease severity. Peripheral blood samples were subjected to routine laboratory tests, while flow cytometry and ELISA were used to measure the lymphocyte subsets and cytokines in blood, respectively. The receiver operating characteristic (ROC) curves were performed to examine the diagnostic of these blood parameters.ResultsSigns of imbalanced lymphocytes composition and hypercytokinemia were observed in HAdV-7-infected patients. The percentages of CD3+ T cells and NK cells were significantly decreased along with the aggravation of the disease, particularly for NK cells and CD4+ T cells. The neutrophil to lymphocyte ratio (NLR) increased significantly in patients with more severe disease. In addition, the levels of serum CXCL10, IL-2 and TNF-α were positively correlated with disease severity, while reduced levels of IFN-γ and IL-10 were found in SP patients. Furthermore, analysis of ROC showed that multiple parameters including the percentage of blood CD3+ cells and serum CXCL10 level could predict the progression of HAdV-7 infection.ConclusionImbalance of immune state with hypercytokinemia occurred during HAdV-7 infection. The percentages of blood immune cells such as CD3+ T cells and the levels of serum cytokines such as CXCL10 showed potential diagnosis values in HAdV-7 infection.

Effect of bariatric surgery procedures on serum cytokine and Nesfatin-1 levels

Backgroundand Purpose: Obesity is known to cause chronic inflammation. We aimed to evaluate the changes in Nesfatin-1 and serum cytokine levels of patients who underwent sleeve gastrectomy or gastric bypass surgery. MethodsA total of 30 patients with BMI>35 and undergoing bariatric surgery were divided in two group, sleeve gastrectomy (SG) (group-1), Roux-en-Y gastric bypass (RYGB) (group-2). Demographic data, weight, BMI, AST, ALT, blood glucose, CRP values, and IL-1β, IFN-α, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 cytokine, and Nesfatin-1 values were noted at the time of hospitalization and in the 6th month postoperative follow-up. ResultsThe mean age of the patients was 37.56 ± 11.73 years, and there were 16 females and 14 males in the study. Body weight and excess body weight change were slightly higher in RYGB patients than in SG patients. In RYGB and SG patients, a significant decrease was found in glucose, AST, ALT, CRP, IL-6, IL-10, and IL-18 values compared to the preoperative period, and serum Nesfatin-1 levels were significantly increased in RYGB patients and not significantly in SG patients. There were also significant decreases in IL-1β levels in RYGB patients. On the other hand, a decrease in cytokines was observed in both surgical methods, except for IL-17A, although it was not significant. ConclusionThe present study showed that there is also a regression in inflammation, which can be associated with NLRP3 inflammasome, due to weight loss after bariatric surgery, more specifically in RYGB.

Clarithromycin-treated chronic spontaneous urticaria with the negative regulation of FcεRΙ and MRGPRX2 activation via CD300f

Mast cells (MCs) are main effector cells in chronic spontaneous urticaria (CSU). Both Fc epsilon RI (FcεRΙ)- and MAS-related G coupled receptor-X2 (MRGPRX2)-mediated MC activations affect CSU course. Leukocyte mono-immunoglobulin-like receptor 3 (CD300f) has been shown to regulate FcεRΙ activation. However, no study has verified CD300f is a target to cure CSU. Therefore this study aimed to verify whether clarithromycin (CLA) regulates FcεRΙ- and MRGPRX2-mediated MC activations via CD300f and shows therapeutic effect on CSU. The target of CLA was verification. CLA inhibited FcεRΙ- and MRGPRX2-mediated MC activations were shown in vivo and in vitro. A single-center, self-comparison study was performed, and CLA-treated CSU was investigated in 28 patients who were not sensitive to the third-generation antihistamines. Serum inflammatory mediators in patients before and after CLA administration were analyzed. CLA effectively inhibited type Ι anaphylactic reactions and pseudo-allergic reactions in mice. Moreover, CLA inhibited FcεRΙ- and MRGPRX2-mediated MC signaling pathway activation. Regulatory effects of CLA were decreased significantly after CD300f knockdown. CLA effectively alleviated the symptoms of wheal and itch and reduced serum cytokine levels in patients. CLA negatively regulated FcεRΙ- and MRGPRX2-mediated MC activation via CD300f and showed significant therapeutic effect on CSU.

Efficacy and safety of apremilast and its impact on serum cytokine levels in patients with Behçet's disease.

To evaluate the long-term clinical efficacy of apremilast in Behçet's disease (BD) and its effect on serum cytokine levels. This study included 15 BD patients who were treated with apremilast. The rates of change in oral and genital ulcers, skin lesions, arthritis, and arthralgia were evaluated every 3months for 12 months. The efficacy of apremilast was compared between patients with and without oral ulcer remission. Changes in the serum levels of interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-10, IL-17A, IL-6, IL-8, and IL-23 between baseline and 3months after apremilast initiation were compared. After 3months, oral and genital ulcers disappeared in most cases. The skin and joint lesions tended to improve for up to 6months; however, recurrence was observed after 9months. The improvement of genital ulcers was earlier in the oral ulcer remission group than the oral ulcer non-remission group, with the genital ulcers disappearing within the first 3months. The baseline levels of serum cytokines, analyzed in seven patients, did not exhibit significant associations with specific organ lesions. After administration of apremilast, the TNF-α and IL-23 levels significantly decreased; however, the IFN-γ, IL-6, IL-8, and IL-10 levels did not show significant changes. The rates of decrease in the serum IL-6, IFN-γ, and IL-10 levels were greater in patients with improved oral ulcers. Modulation of serum cytokine levels with apremilast might underlie the efficacy of apremilast in oral ulcers in BD patients.

Profiling and multivariate analysis of serum cytokines in patients with generalized pustular psoriasis

Introduction: Generalized pustular psoriasis (GPP) is a chronic autoinflammatory disease characterized by fever, erythema, and sterile pustules occurring over large areas of the skin. The immunopathogenesis of GPP remains poorly understood. We aimed to profile serum cytokine levels in patients with GPP and analyze treatment-associated changes in cytokine levels. Methods: Twenty-four patients who were diagnosed with GPP and received drug treatment, together with 28 unaffected controls, were recruited in this study. Levels of 27 cytokines in serum samples from pre- and post-treated patients as well as unaffected controls were assessed using a Bio-Plex multiplex immunoassay. Multivariate analysis of cytokine levels and clinical parameters was conducted. Results: Serum levels of interleukins interleukin (IL)-1β, IL-1Ra, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), IFN-γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1, tumor necrosis factor-α, and vascular endothelial growth factor were significantly elevated (p &lt; .05) in patients with GPP compared with controls. Serum levels of IL-6, G-CSF, IL-8, IFN-γ, IL1-Ra, IL-10, IL-13, and IL-1β were correlated with GPP severity (r &gt; 0.4, p &lt; .001). Following treatment, serum levels of IL-6, IL-7, IL-12, IFN-γ, IL-1β, IL-4, IL-8, IL-10, IL-13, G-CSF, and IP-10 were significantly decreased (p &lt; .05) compared with pretreatment levels. Among these cytokines, levels of IL-6, IL-7, IL-8, IL-12, IL-13, and IP-10 were reduced to normal levels. Conclusion: GPP patients exhibited markedly elevated levels of cytokines and chemokines involved in both type 1 and type 2 immune responses, suggesting hypercytokinemia occurs in GPP patients. IL-6 showed the strongest correlation with GPP disease severity and other clinical parameters such as CRP level and fever, thus representing an index for GPP severity. Our data comprehensively documented the cytokine profiles of GPP patients and may provide insights into GPP pathogenesis.

Medical nutrition therapy versus standard nutrition advice in patients with esophageal cancer: effect on inflammatory cytokines and nutritional status

Rationale: Malnutrition is common in patients with esophageal cancer. The purpose of this study was to compare medical nutrition therapy (MNT) with standard Nutritional Advice (NA) in regards to nutritional status and serum cytokine levels in patients during chemoradiation therapy (CRT).

Cytokines and Water Distribution in Anorexia Nervosa.

In patients with anorexia nervosa (AN), decreased intracellular (ICW), extracellular (ECW), and total body water (TBW) as well as changes in serum cytokine concentrations have been reported. In this exploratory study, we measured body composition and serum cytokine levels in patients with AN (n = 27) and healthy controls (HCs; n = 13). Eating disorder symptom severity was assessed using the Eating Disorder Examination-Questionnaire (EDE-Q). Body composition was determined by bioimpedance analysis (BIA) which provided information on ICW, ECW, and TBW. Following blood collection, 27 cytokines and chemokines were quantified using multiplex ELISA-based technology: Eotaxin, Eotaxin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon- (IFN-) γ, interleukin- (IL-) 1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, interferon γ-induced protein- (IP-) 10, macrophage inflammatory protein- (MIP-) 1α, MIP-1β, monocyte chemoattractant protein- (MCP-) 1, MCP-4, thymus and activation-regulated chemokine (TARC), TNF-α, and TNF-β. ICW, ECW, and TBW volumes were significantly lower in patients with AN than in HCs. In the whole sample, GM-CSF, MCP-4, and IL-4 were positively, whereas IFN-γ, IL-6, and IL-10 were negatively associated with all three parameters of body water. In AN participants, we found a statistically significant negative correlation of IL-10 with ICW, ECW, and TBW. Our results suggest an interaction between body water and the cytokine system. Underlying mechanisms are unclear but may involve a loss of water from the gut, kidneys, or skin due to AN-associated inflammatory processes.

Effects of balneological outpatient treatment on clinical parameters and serum cytokine levels in patients with chronic low back pain: a single-blind randomized controlled trial.

This study aimed to investigate the effects of balneological outpatient treatment (hydrotherapy and peloidotherapy) on clinical status and serum cytokine levels in patients with chronic low back pain (CLBP). Seventy-four patients with CLBP who accepted to participate to the study were randomly divided into two groups. The study group was given ten sessions (in 2 weeks) of hydrotherapy, peloidotherapy, and home exercise, while the control group was given only home exercise. All patients were assessed before and at the end of therapy, at the 1st and 3rd months. The primary outcomes were pain intensity on the visual analog scale (VAS) (VAS-pain, VAS-rest, VAS-exercise) and Oswestry Disability Index (ODI). The secondary outcome measures included patient's and physician's global assessment (VAS-PGA), (VAS-DGA), finger-to-floor distance (FFD), modified Schober test, Short Form-36 (SF-36), and the use of analgesic drug. Venous blood samples were drawn from all patients before/1st day and after therapy/12th day to measure serum interleukin (IL)-6 and IL-10 levels. Significant improvement was observed in the study group in VAS-pain, VAS-rest, VAS-exercise, VAS-PGA, VAS-DGA, ODI, and SF-36 parameters after treatment and improvement maintained for 3 months. In the control group, significant improvement was observed in VAS-pain, VAS-exercise, VAS-PGA, VAS-DGA, and ODI scores on the 12th day and continued for 3 months. Decrease in pain, pain during rest and exercise, modified Schober test, VAS-PGA, VAS-DGA, ODI scores, and the increase in SF-36 pain and general health scores showed superiority in favor of the study group in all evaluations. There was a significant increase in IL-10 values from baseline at the end of treatment in the study group. The use of non-steroidal anti-inflammatory drug (NSAID) was significantly lower in the study group compared with the use of NSAID in the control group in the 3rd month. Balneological outpatient treatment improved clinical status in CLBP patients. Although no significant correlation was clearly determined between IL-10 levels and pain score, this effect might be related to the observed increase in the anti-inflammatory cytokine IL-10 levels that was observed only in the study group.

Cytokine levels in children and adults with wheezing and asthma show specific patterns of variability over time.

Levels of cytokines are used for in-depth characterization of patients with asthma; however, the variability over time might be a critical confounder. To analyze the course of serum cytokines in children, adolescents and adults with asthma and in healthy controls and to propose statistical methods to control for seasonal effects. Of 532 screened subjects, 514 (91·5%) were included in the All Age Asthma Cohort (ALLIANCE). The cohort included 279 children with either recurrent wheezing bronchitis (more than two episodes) or doctor-diagnosed asthma, 75 healthy controls, 150 adult asthmatics and 31 adult healthy controls. Blood samples were collected and 25μl serum was used for analysis with the Bio-Plex Pr human cytokine 27-Plex assay. Mean age, body mass index and gender in the three groups of wheezers, asthmatic children and adult asthmatics were comparable to healthy controls. Wheezers (34·5%), asthmatic children (78·7%) and adult asthmatics (62·8%) were significantly more often sensitized compared to controls (4·5, 22 and 22·6%, respectively). Considering the entire cohort, interleukin (IL)-1ra, IL-4, IL-9, IL-17, macrophage inflammatory protein (MIP)-1- and tumor necrosis factor (TNF)- showed seasonal variability, whereas IL-1β, IL-7, IL-8, IL-13, eotaxin, granulocyte colony-stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, MIP-1 and platelet-derived growth factor (PDGF)-BB did not. Significant differences between wheezers/asthmatics and healthy controls were observed for IL-17 and PDGF-BB, which remained stable after adjustment for the seasonality of IL-17. Seasonality has a significant impact on serum cytokine levels in patients with asthma. Because endotyping has achieved clinical importance to guide individualized patient-tailored therapy, it is important to account for seasonal effects.

Prognostic value of plasminogen activator inhibitor-1 in biomarker exploration using multiplex immunoassay in patients with metastatic renal cell carcinoma treated with axitinib.

Background and AimsVascular endothelial growth factor‐directed therapies play a significant role in patients with metastatic renal cell carcinoma (mRCC). Biomarkers for predicting treatment efficacy and resistance are required to develop personalized medicine. We evaluated multiple serum cytokine levels in patients with mRCC treated with axitinib to explore predictive biomarkers.MethodsFrom September 2012 to October 2015, serum samples were collected from 44 patients with mRCC before treatment and 4 weeks after axitinib initiation. Bio‐Plex Pro Human Cancer Biomarker Panels 1 and 2 were used to measure levels of 34 serum biomarkers related to angiogenesis and cell proliferation.ResultsPatients with partial response or stable disease had significantly decreased serum plasminogen activator inhibitor‐1 (PAI‐1) level from pre‐treatment to 4 weeks after axitinib initiation compared with those with progressive disease (P = .022). The median progression‐free survival (PFS) and median overall survival (OS) in patients with increased serum PAI‐1 level from pre‐treatment to 4 weeks after axitinib initiation were significantly shorter than those with decreased serum PAI‐1 level (P = .027 and P = .026, respectively). Increased serum PAI‐1 level from pre‐treatment to 4 weeks after axitinib initiation was an independent prognostic marker for shorter PFS and OS in multivariate analyses (P = .015 and P = .032, respectively). The immunohistochemical staining intensity of PAI‐1 in tumor specimens was significantly associated with Fuhrman grade and presence of distant metastasis (P = .026 and P = .010, respectively).ConclusionsThe initial change in serum PAI‐1 level in the early stage of axitinib treatment could be a useful prognostic biomarker in patients with mRCC.

Serum cytokine levels in patients with hidradenitis suppurativa vary with race

To the Editor: Hidradenitis suppurativa (HS) is a chronic condition characterized by painful nodules and abscesses in intertriginous areas that can lead to disfigurement. The presumed immunopathogenesis of HS involves an exaggerated response to ruptured follicles. Aberrant cytokine expression has been demonstrated in the serum of patients with HS, specifically, increased serum tumor necrosis factor (TNF)-α,1 interleukin (IL)-17,2 and IL-1β.3 Although biologics targeting TNF-α and IL-1 have shown success, the quest for additional treatment options remains ongoing.