Altered expression of cytokines, chemokines, growth factors, and soluble receptors in patients with colorectal cancer, and correlation with treatment outcome.

Insofar as they play an important role in the pathogenesis of colorectal cancer (CRC), this study analyzes the serum profile of cytokines, chemokines, growth factors, and soluble receptors in patients with CRC and cancer-free controls as possible CRC signatures. Serum levels of 65 analytes were measured in patients with CRC and age- and sex-matched cancer-free controls using the ProcartaPlex Human Immune Monitoring 65-Plex Panel. Of the 65 tested analytes, 8 cytokines (CSF-3, IFN-γ, IL-12p70, IL-18, IL-20, MIF, TNF-α and TSLP), 8 chemokines (fractalkine, MIP-1ß, BLC, Eotaxin-1, Eotaxin-2, IP-10, MIP-1a, MIP-3a), 2 growth factors (FGF-2, MMP-1), and 4 soluble receptors (APRIL, CD30, TNFRII, and TWEAK), were differentially expressed in CRC. ROC analysis confirmed the high association of TNF-α, BLC, Eotaxin-1, APRIL, and Tweak with AUC > 0.70, suggesting theranostic application. The expression of IFN-γ, IL-18, MIF, BLC, Eotaxin-1, Eotaxin-2, IP-10, and MMP1 was lower in metastatic compared to non-metastatic CRC; only AUC of MIF and MIP-1ß were > 0.7. Moreover, MDC, IL-7, MIF, IL-21, and TNF-α are positively associated with tolerance to CRC chemotherapy (CT) (AUC > 0.7), whereas IL-31, Fractalkine, Eotaxin-1, and Eotaxin-2 were positively associated with resistance to CT. TNF-α, BLC, Eotaxin-1, APRIL, and Tweak may be used as first-line early detection of CRC. The variable levels of MIF and MIP-1ß between metastatic and non-metastatic cases assign prognostic nature to these factors in CRC progression. Regarding tolerance to CT, MDC, IL-7, MIF, IL-21, and TNF-α are key when down-regulated or resistant to treatment is observed.

Changes in Levels of Serum Cytokines and Chemokines in Perforated Appendicitis in Children.

Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with clinically suspected appendicitis between 2016 and 2019. Pre-surgical serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular cell-adhesion molecule-1 (ICAM-1), and endothelial selectin (E-selectin) levels were tested from day 1 to day 3 of the disease course. The biomarker values were analyzed and compared between children with normal appendices and appendicitis and those with perforated appendicitis (PA) and non-perforated appendicitis. Among 226 pediatric patients, 106 had non-perforated appendicitis, 102 had PA, and 18 had normal appendices. The levels of all serum proinflammatory biomarkers were elevated in children with acute appendicitis compared with those in children with normal appendices. In addition, the serum IL-6 and TNF-α levels in children with PA were significantly higher, with an elevation in TNF-α levels from days 1 and 2. In addition, serum IL-6 levels increased significantly from days 2 and 3 (both p < 0.05). Serum ICAM-1 and E-selectin levels were elevated in the PA group, with consistently elevated levels within the first three days of admission (all p < 0.05). These results indicate that increased serum levels of proinflammatory biomarkers including IL-6, TNF-α, ICAM-1, and E-selectin could be used as parameters in the prediction and early diagnosis of acute appendicitis, especially in children with PA.

Dysregulation of Plasma Growth Factors and Chemokines in Cocaine Use Disorder: Implications for Dual Diagnosis with Schizophrenia and Antisocial Personality Disorder in an Exploratory Study.

INTRODUCTION: Dual diagnosis in individuals with cocaine use disorders (CUDs) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD). METHODS: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N = 25) or as a dual diagnosis (DD group. N = 30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis. RESULTS: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis. CONCLUSIONS: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics.

Cytokine and chemokine profiles in the sera of COVID-19 patients with different stages of severity.

INTRODUCTION: COVID-19 is a viral infection that disturbs the host's immune system and causes an overproduction of cytokines leading to a cytokine storm. The present study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with COVID-19 disease severity. METHODS: The serum levels of 89 patients with different degrees of COVID-19 disease severity [asymptomatic (n = 14), moderate (n = 14), severe (n = 30), and critical (n = 31)] and 14 healthy individuals were tested for a panel of 27 cytokines and chemokines using Luminex assay (27 Bio­Plex Pro Human Cytokine, Bio-rad™). RESULTS: IL-12, IL-2 and IL-13, as well as IL-17 and GM-CSF were clearly undetectable in asymptomatic patients. IL-8 levels were higher in asymptomatic compared with other groups. Very high levels of IL-6, IL-10 and the chemokines MIP-1α, MCP-1 and IP10 were associated with disease progression, while IL-4 tends to decrease with disease severity. CONCLUSION: Our study provides more evidence that excessive cytokine synthesis is linked to the disease progression.

Utility of serum chemokine-like factor 1 as a biomarker of severity and prognosis after severe traumatic brain injury: A prospective observational study.

BACKGROUND: Chemokine-like factor 1 (CKLF1) may be involved in the inflammatory response and secondary brain injury after severe traumatic brain injury (sTBI). We determined serum CKLF1 levels of sTBI patients to further investigate the correlation of CKLF1 levels with disease severity, functional prognosis, and 180-day mortality of sTBI. METHODS: Serum CKLF1 levels were measured at admission in 119 sTBI patients and at entry into study in 119 healthy controls. Serum CKLF levels of 50 patients were also quantified at days 1-3, 5, and 7 after admission. Glasgow coma scale (GCS) scores and Rotterdam computerized tomography (CT) classification were utilized to assess disease severity. Extended Glasgow outcome scale (GOSE) scores were recorded to evaluate function prognosis at 180 days after sTBI. Relations of serum CKLF1 levels to 180-day poor prognosis (GOSE scores of 1-4) and 180-day mortality were analyzed using univariate analysis, followed by multivariate analysis. Receiver-operating characteristic (ROC) curve was built to investigate prognostic predictive capability. RESULTS: Serum CKLF1 levels of sTBI patients increased at admission, peaked at day 2, and then gradually decreased; they were significantly higher during the 7 days after sTBI than in healthy controls. Differences of areas under ROC curve (areas under the curve [AUCs]) were not significant among the six time points. Multivariate analysis showed that serum CKLF1 levels were independently correlated with GCS scores, Rotterdam CT classification, and GOSE scores. Serum CKLF1 levels were significantly higher in non-survivors than in survivors and in poor prognosis patients than in good prognosis patients. Serum CKLF1 levels independently predicted 180-day poor prognosis and 180-day mortality, and had high 180-day prognosis and mortality predictive abilities, and their AUCs were similar to those of GCS scores and Rotterdam CT classification. Combination model containing serum CKLF1, GCS scores, and Rotterdam CT classification performed more efficiently than any of them alone in predicting mortality and poor prognosis. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. CONCLUSION: Serum CKLF1 levels are significantly associated with disease severity, poor 180-day prognosis, and 180-day mortality in sTBI patients. Hence, complement CKLF1 may serve as a potential prognostic biomarker of sTBI.

Multi-cohort study on cytokine and chemokine profiles in the progression of COVID-19.

Various substances in the blood plasma serve as prognostic indicators of the progression of COVID-19. Consequently, multi-omics studies, such as proteomic and metabolomics, are ongoing to identify accurate biomarkers. Cytokines and chemokines, which are crucial components of immune and inflammatory responses, play pivotal roles in the transition from mild to severe illness. To determine the relationship between plasma cytokines and the progression of COVID-19, we used four study cohorts to perform a systematic study of cytokine levels in patients with different disease stages. We observed differential cytokine expression between patients with persistent-mild disease and patients with mild-to-severe transformation. For instance, IL-4 and IL-17 levels significantly increased in patients with mild-to-severe transformation, indicating differences within the mild disease group. Subsequently, we analysed the changes in cytokine and chemokine expression in the plasma of patients undergoing two opposing processes: the transition from mild to severe illness and the transition from severe to mild illness. We identified several factors, such as reduced expression of IL-16 and IL-18 during the severe phase of the disease and up-regulated expression of IL-10, IP-10, and SCGF-ß during the same period, indicative of the deterioration or improvement of patients' conditions. These factors obtained from fine-tuned research cohorts could provide auxiliary indications for changes in the condition of COVID-19 patients.

Differences in mid-gestational and early postnatal neonatal cytokines and chemokines are associated with patterns of maternal autoantibodies in the context of autism.

Associations between maternal immune dysregulation (including autoimmunity and skewed cytokine/chemokine profiles) and offspring neurodevelopmental disorders such as autism have been reported. In maternal autoantibody-related autism, specific maternally derived autoantibodies can access the fetal compartment to target eight proteins critical for neurodevelopment. We examined the relationship between maternal autoantibodies to the eight maternal autoantibody-related autism proteins and cytokine/chemokine profiles in the second trimester of pregnancy in mothers of children later diagnosed with autism and their neonates' cytokine/chemokine profiles. Using banked maternal serum samples from 15 to 19 weeks of gestation from the Early Markers for Autism Study and corresponding banked newborn bloodspots, we identified three maternal/offspring groups based on maternal autoantibody status: (1) mothers with autoantibodies to one or more of the eight maternal autoantibody-related autismassociated proteins but not a maternal autoantibody-related autism-specific pattern, (2) mothers with a known maternal autoantibody-related autism pattern, and (3) mothers without autoantibodies to any of the eight maternal autoantibody-related autism proteins. Using a multiplex platform, we measured maternal second trimester and neonatal cytokine/chemokine levels. This combined analysis aimed to determine potential associations between maternal autoantibodies and the maternal and neonatal cytokine/chemokine profiles, each of which has been shown to have implications on offspring neurodevelopment independently.

Cytokines and chemokines in patients with chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: A systematic review.

Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3-71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.

A nationwide study on immunosenescence biomarkers profile in older adults: ELSI-Brazil.

Immunosenescence is a phenomenon caused by changes in the immune system, and part of these changes involves an increase in circulating immunological biomarkers, a process known as "Inflammaging." Inflammaging can be associated with many diseases related to older people. As the older population continues to grow, understanding changes in the immune system becomes essential. While prior studies assessing these alterations have been conducted in countries with Caucasian populations, this investigation marks a pioneering effort. The object of the study is to describe for the first time that the distribution of cytokines, chemokines, and growth factors serum levels, assessed by Luminex platform, has been examined in a Brazilian population-based study of older adult females and males by age. Blood samples from 2111 participants (≥50 years old) were analyzed at the baseline (2015/2016) of the ELSI-Brazil study. The exploratory variables considered in the study were age, sex, educational level, residence area, geographic region, alcohol and smoking consumption, physical activity, and self-reported medical diagnoses of hypertension, diabetes, asthma, arthritis, and cancer. The association between serum biomarker levels and age was assessed by a quantile regression model adjusted in the total population and stratified by sex. The significance level considered in the analysis was 0.05. The mean age of the participants was 62.9 years, with a slight majority of female (52.7 %). Differences were found between the sexes in the median circulating levels of the CCL11, CXCL10, and FGF biomarkers. Eight biomarkers showed significant associations with age, including the pro-inflammatory CXCL10, TNF-α, IL-6, IL-17, and IL-2; and type 2/regulatory CCL11 and IL-4, showing positive associations, and anti-inflammatory IL-1Ra showing a negative association. The results suggest similar associations between the sexes, revealing an inflammatory profile characterized by types 1 and 2. Remarkably, these findings reinforce the concept of the Inflammaging process in Brazilian population. These findings add novel insights to about the immunosenescence aspects in middle-income countries and help define biomarkers capable of monitoring inflammation in older adults.

Predictive value of glycoprotein DKK3 for early neurological deterioration after ischemic stroke.

OBJECTIVE: To explore the value of serum Dickkopf-3 (sDKK3) in predicting Early Neurological Deterioration (END) and in-hospital adverse outcomes in acute ischemic stroke (AIS) patients. METHODS: AIS patients (n = 200) were included and assessed by the National Institutes of Health Stroke Rating Scale. Serum Dkk3 levels were assessed by ELISA. END was defined as an increase of ≥ 4 points in NIHSS score within 72h. The biological threshold of sDKK3 level and END occurrence were predicted based on X-tile software. Primary outcomes were END and all-cause death, and the secondary outcome was ICU admission during hospitalization. The logistic regression model and Cox risk regression model were applied to evaluate the relationship between DKK3 level and END incidence, all-cause in-hospital mortality, and in-hospital adverse outcomes (ICU admission). RESULTS: During hospitalization, the incidence of END in patients with AIS was 13.0 %, and the mortality rate within 7 days after END was 11.54 % (3/26). In patients below the serum DKK3 cutoff (93.0 pg/mL), the incidence of END was 43.5 % (20/48). Patients with lower sDKK3 levels were associated with a 1.188-fold increased risk of developing END (OR = 1.188, 95 % CI 1.055‒1.369, p < 0.0001). However, there was no significant association with admission to the ICU. sDKK3 below the threshold (93.0 pg/mL) was a risk factor for death. CONCLUSION: Predictive threshold levels of serum DKK3 based on X-tile software may be a potential predictive biomarker of in-hospital END in patients with AIS, and low levels of DKK3 are independently associated with increased in-hospital mortality.

Prognostic value of angiogenic T cells in hepatitis B-induced liver cirrhosis.

This study was performed to investigate the frequency of angiogenic T cells (CD4+ Tang cells) among CD4+ T cells in patients with hepatitis B-induced liver cirrhosis (HBV-LC) and to evaluate the predictive role of these cells in the clinical outcome. In total, 185 patients with HBV-LC were recruited to measure the frequency of CD4+ Tang cells and chemokine levels using flow cytometry. RESULTS: There was 11.4% of death after 3-momth follow-up. The AUC for the ability of the frequency of CD4+ Tang cell to predict death was 0.724 (higher than those for the MELD score, FIB-4 score, and Child-Pugh classification). Cox regression analysis revealed an association between the frequency of CD4+ Tang cells and a 3-month survival chance. CONCLUSIONS: The lower frequency of CD4+ T ang cells was correlated with the severity of HBV-LC and may serve as a prognostic predictor.

Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy.

Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed. Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tumor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival. Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of responding patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling tertiary lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival. Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients. Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomarkers needing validation and become hypothesis generating for experimental research.

The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease.

Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role of the chemerin/CMKLR1 axis in GvHD was investigated using Cmklr1-KO mice. WT mice transplanted with an allogeneic graft from Cmklr1-KO donors (t-KO) had worse survival and more severe GvHD. Histological analysis demonstrated that the gastrointestinal tract was the organ mostly affected by GvHD in t-KO mice. The severe colitis of t-KO mice was characterized by massive neutrophil infiltration and tissue damage associated with bacterial translocation and exacerbated inflammation. Similarly, Cmklr1-KO recipient mice showed increased intestinal pathology in both allogeneic transplant and dextran sulfate sodium-induced colitis. Notably, the adoptive transfer of WT monocytes into t-KO mice mitigated GvHD manifestations by decreasing gut inflammation and T cell activation. In patients, higher chemerin serum levels were predictive of GvHD development. Overall, these results suggest that CMKLR1/chemerin may be a protective pathway for the control of intestinal inflammation and tissue damage in GvHD.

Identification of host biomarkers from dried blood spots for monitoring treatment response in extrapulmonary tuberculosis.

There is a lack of objective tools for monitoring treatment response in extrapulmonary tuberculosis (EPTB). This study aimed to explore the utility of inflammatory biomarkers from the dry blood spots (DBS) as a tool for monitoring treatment response in EPTB. In a prospective cohort study, 40 inflammatory biomarkers were investigated in DBS samples from 105 EPTB cases using a Luminex platform. The samples were taken before, and, at the end of the 2nd and 6th months of treatment. A total of 11 inflammatory host biomarkers changed significantly with treatment in all EPTB patients. CXCL9/MIG, CCL20, CCL23, CXCL10/IP-10, CXCL1, CXCL2, and CXCL8 significantly declined in our cohort of EPTB (48 TB pleuritis and 57 TB lymphadenitis) patients at both time points. A biosignature consisting of MIG, CCL23, and CXCL2, corresponded with the treatment response in 81% of patients in the 2nd month and 79% of patients at the end of treatment. MIG, CCL23, IP-10, and CXCL2 changed significantly with treatment in all patients including those showing partial clinical response at the 2nd month of treatment. The changes in the levels of inflammatory biomarkers in the DBS correspond with the treatment success and can be developed as a routine test in low-resource settings.

Hsp90 as a Myokine: Its Association with Systemic Inflammation after Exercise Interventions in Patients with Myositis and Healthy Subjects.

Compelling evidence supports the health benefits of physical exercise on the immune system, possibly through the molecules secreted by the skeletal muscles known as myokines. Herein, we assessed the impact of exercise interventions on plasma Heat shock protein 90 (Hsp90) levels in 27 patients with idiopathic inflammatory myopathies (IIM) compared with 23 IIM patients treated with standard-of-care immunosuppressive therapy only, and in 18 healthy subjects undergoing strenuous eccentric exercise, and their associations with the traditional serum markers of muscle damage and inflammation. In contrast to IIM patients treated with pharmacotherapy only, in whom we demonstrated a significant decrease in Hsp90 over 24 weeks, the 24-week exercise program resulted in a stabilization of Hsp90 levels. These changes in Hsp90 levels were associated with changes in several inflammatory cytokines/chemokines involved in the pathogenesis of IIM or muscle regeneration in general. Strenuous eccentric exercise in healthy volunteers induced a brief increase in Hsp90 levels with a subsequent return to baseline levels at 14 days after the exercise, with less pronounced correlations to systemic inflammation. In this study, we identified Hsp90 as a potential myokine and mediator for exercise-induced immune response and as a potential biomarker predicting improvement after physiotherapy in muscle endurance in IIM.

A Comparative Study of the Plasma Chemokine Profile in COVID-19 Patients Infected with Different SARS-CoV-2 Variants.

BACKGROUND: Infection caused by SARS-CoV-2 mostly affects the upper and lower respiratory tracts and causes symptoms ranging from the common cold to pneumonia with acute respiratory distress syndrome. Chemokines are deeply involved in the chemoattraction, proliferation, and activation of immune cells within inflammation. It is crucial to consider that mutations within the virion can potentially affect the clinical course of SARS-CoV-2 infection because disease severity and manifestation vary depending on the genetic variant. Our objective was to measure and assess the different concentrations of chemokines involved in COVID-19 caused by different variants of the virus. METHODS: We used the blood plasma of patients infected with different variants of SARS-CoV-2, i.e., the ancestral Wuhan strain and the Alpha, Delta, and Omicron variants. We measured the concentrations of 11 chemokines in the samples: CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, and CX3CL1/Fractalkine. RESULTS: We noted a statistically significant elevation in the concentrations of CCL2/MCP-1, CXCL8/IL-8, and CXCL1/IP-10 independently of the variant, and a drop in the CCL22/MDC concentrations. CONCLUSIONS: The chemokine concentrations varied significantly depending on the viral variant, leading us to infer that mutations in viral proteins play a role in the cellular and molecular mechanisms of immune responses.

Serum from COVID-19 patients early in the pandemic shows limited evidence of cross-neutralization against variants of concern.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a variety of clinical symptoms ranging from no or mild to severe disease. Currently, there are multiple postulated mechanisms that may push a moderate to severe disease into a critical state. Human serum contains abundant evidence of the immune status following infection. Cytokines, chemokines, and antibodies can be assayed to determine the extent to which a patient responded to a pathogen. We examined serum and plasma from a cohort of patients infected with SARS-CoV-2 early in the pandemic and compared them to negative-control sera. Cytokine and chemokine concentrations varied depending on the severity of infection, and antibody responses were significantly increased in severe cases compared to mild to moderate infections. Neutralization data revealed that patients with high titers against an early 2020 SARS-CoV-2 isolate had detectable but limited neutralizing antibodies against the emerging SARS-CoV-2 Alpha, Beta and Delta variants. This study highlights the potential of re-infection for recovered COVID-19 patients.

Circulating chemerin levels in metabolic-associated fatty liver disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Chemerin is a brand-new adipokine that has been linked to both inflammation and metabolic dysfunction. Even though a rising number of studies have connected chemerin to metabolic-associated fatty liver disease (MAFLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), this association has been controversial. METHODS: A comprehensive literature search was undertaken up to February 1, 2022, in the PubMed, Embase, Web of Science, CNKI, WANFANG, and CBM library databases. Circulating chemerin levels were obtained and summarized using the standardized mean difference (SMD) and 95% confidence interval (CI). Subgroup and meta-regression analyses were conducted to examine the possibility of heterogeneity. RESULTS: A total of 17 studies involving 2580 participants (1584 MAFLD patients and 996 controls) evaluated circulating chemerin levels in patients with MAFLD. The present study showed that higher chemerin levels were found in patients with MAFLD (SMD: 1.32; 95% CI: 0.29, 2.35) and nonalcoholic fatty liver (NAFL) (SMD: 0.75; 95% CI: 0.01, 1.50) compared to controls. However, circulating chemerin levels did not differ significantly in the following comparisons: nonalcoholic steatohepatitis (NASH) patients and controls (SMD: 0.75; 95% CI: -0.52, 2.03); NASH patients and NAFL patients (SMD: 0.16; 95% CI: -0.39, 0.70); moderate to severe steatosis and mild steatosis (SMD: 0.55; 95% CI: -0.59, 1.69); present liver fibrosis and absent liver fibrosis (SMD: 0.66; 95% CI: -0.42, 1.74); present lobular inflammation and absent lobular inflammation (SMD: 0.45; 95% CI: -0.53, 1.42); and present portal inflammation and absent portal inflammation (SMD: 1.92; 95% CI: -0.85, 4.69). CONCLUSIONS: Chemerin levels were considerably greater in patients with MAFLD than in controls, despite the fact that they were not significantly linked to different liver tissue lesions of MAFLD. In different subtypes of MAFLD, in comparison to healthy controls, the chemerin levels of NAFL patients were higher, whereas, there was no obvious difference in chemerin levels between NASH patients and controls. It is possible that chemerin will be used as a biomarker in the future to track the development and progression of MAFLD.

Serum soluble mediator waves and networks along healthy ageing.

The ageing process is a complex phenomenon that impacts the immune system, leading to changes in the pattern of serum soluble mediators. In the present study, the serum levels of several chemokines, pro-inflammatory/regulatory cytokines and growth factors were quantified by high-throughput microbeads array in serum samples from 541 healthy subjects at distinct age ranges (3Yrs to >70Yrs). A broad increase in serum soluble mediators was observed at 6-10Yrs with subsequent decline at 11-20Yrs and 21-30Yrs followed by a second round of upregulation starting at 31-40Yrs, with a large increase at 51-60Yrs and a marked decline at age >70Yrs. Heatmap and signatures of serum soluble mediators demonstrated a bimodal profile with one peak at 6-10Yrs and a second wave around 61-70Yrs. A universal decline was observed later at age >70Yrs. In males, the second wave started earlier at 31-40Yrs with a peak at 51-60Yrs and a further smooth decline towards >70Yrs. Conversely, in females, the first peak extended from 3-5Yrs to 6-10Yrs and the second wave starting around 41-50Yrs with a peak at 61-70Yrs followed by a sharp decline at >70Yrs. Overall, CCL11, CXCL8, IL-1ß, IL-6 were underscored as universal age-related biomarkers with higher levels observed at later age ranges (after 31-40Yrs) and TNF with increased levels starting at early age ranges. Data analysis demonstrated that the highest neighborhood connectivity amongst soluble mediators occurred at 3-5Yrs, with distinct declining and strengthening rhythm in males and females. Notably, rebuilding re-arrangements were usually earlier and more frequent in females (at 11-20Yrs, 51-60Yrs and >70Yrs) than in males (at 21-30Yrs, 61-70Yrs). Overall, this study provided a comprehensive landscape of evidence portrayed by distinct waves, rhythms and dynamic network connectivity along healthy ageing with differences in magnitude and timing reported for sexes.

Diagnostic and Prognostic Biomarkers of Coronavirus Disease 2019 in Children.

Predictors of early diagnosis and severe infection in children with coronavirus disease 2019 (COVID-19), which has killed more than 4 million people worldwide, have not been identified. However, some biomarkers, including cytokines and chemokines, are associated with the diagnosis, pathogenesis and severity of COVID-19 in adults. We examined whether such biomarkers can be used to predict the diagnosis and prognosis of COVID-19 in pediatric patients. Eighty-nine children were included in the study, comprising three patient groups of 69 patients (6 severe, 36 moderate and 27 mild) diagnosed with COVID-19 by real-time polymerase chain reaction observed for 2-216 months and clinical findings and 20 healthy children in the same age group. Hemogram, coagulation, inflammatory parameters and serum levels of 16 cytokines and chemokines were measured in blood samples and were analyzed and compared with clinical data. Interleukin 1-beta (IL-1ß), interleukin-12 (IL-12) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in the COVID-19 patients (p = 0.035, p = 0.006 and p < 0.001). Additionally, D-dimer and IP-10 levels were higher in the severe group (p = 0.043 for D-dimer, area under the curve = 0.743, p = 0.027 for IP-10). Lymphocytes, C-reactive protein and procalcitonin levels were not diagnostic or prognostic factors in pediatric patients (p = 0.304, p = 0.144 and p = 0.67). Increased IL-1ß, IL-12 and IP-10 levels in children with COVID-19 are indicators for early diagnosis, and D-dimer and IP-10 levels are predictive of disease severity. In children with COVID-19, these biomarkers can provide information on prognosis and enable early treatment.