Aqueous humor cytokine levels are associated with the severity of visual field defects in patients with primary open-angle glaucoma.

BACKGROUND: To evaluate the aqueous humor (AH) levels of cytokines in primary open-angle glaucoma (POAG) patients and cataract patients. METHODS: Thirty-eight POAG patients and 26 cataract patients were recruited. Peripheral blood (PB) was collected from each subject. The POAG group was divided into 2 subgroups according to the severity of visual field defects. The cutoff point of the mean deviation (MD) of the visual field was -12 dB. AH was obtained at the time of anterior chamber puncture during cataract or glaucoma surgery by using a 27-gauge needle attached to a microsyringe. AH and PB levels of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta2 (TGF-ß2) and IL-4 were assayed by enzyme-linked immunosorbent assay. Postoperative intraocular pressures (IOPs) of POAG patients were recorded during the follow-up period. RESULTS: TNF-α and TGF-ß2 showed significantly higher AH levels in the POAG group than in the cataract group (P < 0.001 and P = 0.001, respectively). For the POAG group, preoperative IOPs were significantly positively correlated with AH levels of TNF-α (r2 = 0.129, P = 0.027) and TGF-ß2 (r2 = 0.273, P = 0.001). AH levels of TGF-ß2 were significantly different among cataract patients, POAG patients with MD> -12 dB and POAG patients with MD≤ -12 dB (P = 0.001). AH levels of TNF-α were significantly positively associated with IOP reduction after trabeculectomy (P = 0.025). AH and PB levels of cytokines were not related to the long-term success of trabeculectomy. CONCLUSION: The levels of TNF-α and TGF-ß2 showed different profiles in POAG patients and cataract patients. AH levels of TGF-ß2 were correlated with the severity of glaucomatous neuropathy in POAG patients. The findings suggest possible roles for cytokines in the pathogenesis and development of POAG.

[Detection Value of EB Virus DNA, IL-2, and IL-6 Level in Peripheral Blood of Children with Infectious Mononucleosis].

OBJECTIVE: To investigative the detection value of EB virus DNA (EBV-DNA), interleukin-2 (IL-2), and interleukin-6 (IL-6) level in peripheral blood of children with infectious mononucleosis (IM). METHODS: A total of 59 children clinically confirmed with IM in Anhui Provincial Children's Hospital from January 2018 to September 2020 were enrolled as IM group, while other 30 healthy children undergoing physical examination during the same period were enrolled as healthy group. The level of EBV-DNA load, IL-2, and IL-6 were compared between the two groups, and their diagnostic values for IM children were explored. According to the median level of EBV-DNA load, positive children were divided into high viral load group and low viral load group. The hepatomegaly and splenomegaly, and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-2, and IL-6 were compared between the two groups. The relationship between EBV-DNA load and IL-2, IL-6 levels were explored. RESULTS: The positive rate of EBV-DNA was 67.80% in IM group, which was significantly higher than 10.00% in healthy group (P<0.001), and the levels of serum IL-2 and IL-6 were also significantly higher than healthy group (P<0.001). The results of ROC curve analysis showed that AUC of IL-2 combined with IL-6 and EBV-DNA load was 0.948, which was significantly greater than that of IL-2, IL-6, and EBV-DNA load alone (0.847, 0.728, 0.789) (P<0.001). The cut-off value of IL-2 and IL-6 was 15.545 pg/ml and 56.560 pg/ml, respectively. Both the proportions of cases with moderate to severe hepatomegaly and splenomegaly in high viral load group were significantly higher than those in low viral load group (P<0.01, P<0.05). The levels of ALT, AST, and IL-2 in high viral load group were significantly higher than those in low viral load group (P<0.001), as well as IL-6 (P<0.01). In high and low viral load groups, EBV-DNA load was positively correlated with IL-2 and IL-6 (in high viral load group, rIL-2=0.598, rIL-6=0.416; in low viral load group, rIL-2=0.621, rIL-6=0.527, P<0.001). CONCLUSION: The detection of EBV-DNA load combined with IL-2 and IL-6 can improve the diagnostic accuracy of IM, and EBV-DNA load, IL-2 and IL-6 levels are related to the disease progression.

White Blood Cell Count and Serum Cytokine Profile in Tropical Hardwood Workers in Kumasi.

Background: Occupational exposure to wood dust particles has long been reported of its associated varying degrees of negative health effects due to different extractive chemicals present in the various timber species. However, tropical hardwood is also reported to have higher levels of extractive chemicals of antihistamine, antioxidant, and anti-inflammatory properties. In Ghana, woodworkers have for years been exposed to wood dust from mixed tropical hardwood species, with little or no protective equipment such as nose masks, yet with less significant respiratory conditions. This study seeks to investigate the serum cytokine profile in tropical hardwood workers in Kumasi to provide a better understanding of the immunoregulatory pattern activated in the woodworkers. Method: The study was carried out among woodworkers, teachers, and security men located in Kumasi. A cross-sectional sampling of adult male workers was selected to participate in the study (86 woodworkers and 89 nonwoodworkers). Participants donated blood collected by venepuncture into EDTA tubes and spun to separate serum for cytokine assay. Cytokines including IFN-gamma, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-17 were assayed using the Human Premixed Multianalyte Kit (R&D System, Inc., Minneapolis, USA) following the manufacturer's procedure. The cytokine levels were quantified using the Luminex∗200 analyser. Results: The mean concentration levels for the various cytokines were significantly different (p < 0.05) between woodworkers and nonwoodworkers except IL-2. There were significantly increased levels of Th1 and Th2 cytokines expressed in the woodworkers more than the nonwoodworkers. Conclusions: The results from this study reveal that exposed woodworkers of mixed tropical hardwood species show a high level of Th1 and Th2 cytokines in their serum than nonwoodworkers.

Microwave ablation of non-small cell lung cancer tumors changes plasma levels of cytokines IL-2 and IFN-γ.

Background: Combined therapy with immune checkpoint inhibitors (ICIs) and microwave ablation (MWA) is known to improve outcome in non-small cell lung cancer (NSCLC). However, the mechanism underlying the synergistic effect of these two treatments is unknown. Tumor immune microenvironment is known to affect the efficacy of ICI. Therefore, in the present study, we evaluated changes in the levels of peripheral cytokines at 48 h and 1-month post-ablation in patients with NSCLC. Materials and Methods: A total of 44 patients with primary NSCLC were retrospectively enrolled. All patients underwent MWA of the primary tumors. Plasma samples were collected pre- and post-ablation to examine the levels of various cytokines, including interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor (TNF)-α, and interferon-gamma (IFN-γ). Results: Although the levels of the majority of cytokines remained within normal range, levels of IL-2 and IFN-γ were significantly decreased at 48 h post-ablation and increased at 1-month post-ablation. In the subgroup analyses, changes in IL-2 and IFN-γ levels were commonly identified. Moreover, the Eastern Cooperative Oncology Group status, sex, pathology type, tumor site, and tumor size were associated with cytokines' levels pre-ablation or post-ablation. Conclusion: MWA of NSCLC tumors influenced the plasma levels of cytokines IL-2 and IFN-γ.

Characterization of memory T cell subsets and common γ-chain cytokines in convalescent COVID-19 individuals.

T cells are thought to be an important correlates of protection against SARS-CoV2 infection. However, the composition of T cell subsets in convalescent individuals of SARS-CoV2 infection has not been well studied. The authors determined the lymphocyte absolute counts, the frequency of memory T cell subsets, and the plasma levels of common γ-chain in 7 groups of COVID-19 individuals, based on days since RT-PCR confirmation of SARS-CoV-2 infection. The data show that both absolute counts and frequencies of lymphocytes as well as, the frequencies of CD4+ central and effector memory cells increased, and the frequencies of CD4+ naïve T cells, transitional memory, stem cell memory T cells, and regulatory cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. In addition, the frequencies of CD8+ central memory, effector, and terminal effector memory T cells increased, and the frequencies of CD8+ naïve cells, transitional memory, and stem cell memory T cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. The plasma levels of IL-2, IL-7, IL-15, and IL-21-common γc cytokines started decreasing from Days 15-30 till Days 151-180. Severe COVID-19 patients exhibit decreased levels of lymphocyte counts and frequencies, higher frequencies of naïve cells, regulatory T cells, lower frequencies of central memory, effector memory, and stem cell memory, and elevated plasma levels of IL-2, IL-7, IL-15, and IL-21. Finally, there was a significant correlation between memory T cell subsets and common γc cytokines. Thus, the study provides evidence of alterations in lymphocyte counts, memory T cell subset frequencies, and common γ-chain cytokines in convalescent COVID-19 individuals.

Tertiary lymphoid structures and their association to immune phenotypes and circulatory IL2 levels in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is usually unresponsive to immunotherapeutic approaches. However, tertiary lymphoid structures (TLS) are associated with favorable patient outcomes in PDA. A better understanding of the B cell infiltrate and biological features of TLS formation is needed to further explore their potential and improve patient management. We analyzed tumor tissues (n = 55) and corresponding blood samples (n = 51) from PDA patients by systematical immunohistochemistry and multiplex cytokine measurements. The tissue was compartmentalized in "tumor" and "stroma" and separately examined. Clinical patient information was used to perform survival analyses. We found that the mere number of B cells is not associated with patient survival, but formation of TLS in the peritumoral stroma is a prognostic favorable marker in PDA patients. TLS-positive tissues show a higher density of CD8+ T cells and CD20+ B cells and a higher IL2 level in the peritumoral stroma than tissues without TLS. Compartmental assessment shows that gradients of IL2 expression differ with regard to TLS formation: TLS presence is associated with higher IL2 levels in the stromal than in the tumoral compartment, while no difference is seen in patients without TLS. Focusing on the stroma-to-serum gradient, only patients without TLS show significantly higher IL2 levels in the serum than in stroma. Finally, low circulatory IL2 levels are associated with local TLS formation. Our findings highlight that TLS are prognostic favorable and associated with antitumoral features in the microenvironment of PDA. Also, we propose easily accessible serum IL2 levels as a potential marker for TLS prediction.

Phasic firing of dopaminergic neurons in the ventral tegmental area triggers peripheral immune responses.

Dopaminergic neurons in the ventral tegmental area (VTA) play a crucial role in the processing of reward-related information. Recent studies with pharmacological manipulations of VTA neuronal activity demonstrated a VTA-induced immunoenhancement in peripheral organs. Here, to examine the detailed physiological dynamics, we took an optogenetic approach in which VTA dopaminergic neurons were selectively activated with millisecond precision. Optogenetic phasic, rather than tonic, stimulation of VTA dopaminergic neurons increased serum cytokine levels, such as IL-2, IL-4 and TNF-α. These results provide direct evidence to link dopaminergic neuronal phasic firing to peripheral immunity. Next, we tested whether cytokine induction in male mice was boosted by female encounters, a natural condition that induces increased active VTA neurons and gamma power. Female encounters increased serum IL-2 levels, which were abolished by pharmacological inhibition of VTA neuronal activity. Taken together, our results highlight the importance of the brain reward system in the treatment and management of immune-related disorders.

Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity.

INTRODUCTION: Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS: Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. RESULTS: Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION: Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

Serum JAK/STAT profile is related to the IL expression but not with the outcome in pancreatic adenocarcinoma patients.

Current genetic characterization of pancreatic ductal adenocarcinoma (PDAC) does not integrate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. The JAK/STAT pathway is an important factor of cytokine-mediated cancer inflammation, but its relationship with pancreatic carcinogenesis and the role of potential biomarkers is not established yet. Our study aimed to assess the significance of serum levels of JAK/STAT3 expression and inflammatory cytokines in PDAC in relation to the clinicopathological features and prognosis. This prospective cohort study included patients with proven adenocarcinoma and a matched group of controls without any malignancies. There were evaluated the serum expression of IL2, 6, 8, 17, JAK2, and STAT3 by ELISA assays in these two groups. The PDAC patients were followed up for 24 months. A Cox regression multivariate analysis model was used to determine factors influencing survival. The study comprised 56 patients with PDAC and 56 controls. The upregulated serum JAK2/STAT3 or cytokines were present in about half of the patients with PDAC, similar to controls. The expression of JAK2 in serum of PDAC patients was significantly associated with the expression of IL2 (p=0.03) and IL6 (p=0.02) but not with survival or metastasis development. Only age and the presence of lymph node metastases were associated with reduced survival in multivariate analyses. The STAT 3/JAK2 expression, although correlated with inflammatory status (IL2, IL6) was not overexpressed in PDAC compared to controls and proved no prognostic value.

The Role of Serum Th1, Th2, and Th17 Cytokines in Patients with Alopecia Areata: Clinical Implications.

Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17E, IL-31 and IL-33) and Th17 (IL-17, IL-17F, IL-21, IL-22, IL-23 and TGF-ß) cytokines was observed in patients with alopecia areata. Positive correlations between the severity of alopecia areata and an increased serum level of various cytokines including IL-2, TNF, IL-12, IL-17, and IL-17E were reported in the literature. An increased serum level of numerous cytokines, such as IL-2, IL-6, TNF, IL-12, IL-17E, and IL-22, was described as positively correlated with the duration of the disease. Moreover, it was shown that increased pre-treatment serum level of IL-12 was a positive, while increased serum levels of IL-4 and IL-13 were negative prognostic markers for the efficacy of diphenylcyclopropenone. In conclusion, alopecia areata is associated with the dysregulation of systemic Th1, Th2 and Th17 cytokines with their role in the pathogenesis, clinical manifestations and prognosis of the disease. Available data indicate the most significant role of serum IL-2, TNF, IL-12, IL-17, and IL-17E as markers of disease activity. The serum levels IL-4, IL-12 and IL-13 may be useful as potential predictors of diphenylcyclopropenone efficacy.

Myeloid dendritic cells in severe aplastic anemia patients exhibit stronger phagocytosis.

BACKGROUND: A deeper understanding of the pathogenesis of severe aplastic anemia (SAA) is urgently warranted to achieve better therapeutic effects. The objective of this study was to investigate the phagocytosis of myeloid dendritic cell (mDC) in SAA patients. METHODS: Myeloid dendritic cells were induced in vitro from bone marrow mononuclear cells from 26 SAA patients and 12 normal controls (HCs). The phagocytosis of mDCs was detected by flow cytometry using FITC-Dextran (40KD), and its correlation with the immune status and severity of the disease was analyzed. RESULTS: The phagocytosis of mDC from untreated SAA patients was significantly stronger than that from complete remission group and HC group (p < 0.05). There was no statistical difference between the latter two groups (p > 0.05). The phagocytosis of mDC from SAA patients correlated positively with the concentration of interleukin (IL)-2 (r = 0.389, p < 0.05), and IL-4 (r = 0.556, p < 0.05), negatively with CD4+ /CD8+ ratio (r = -0.421, p < 0.05). It also had negative correlations with the level of hemoglobin (r = -0.393, p < 0.05), white blood cell (r = -0.436, p < 0.05), platelet (r = -0.431, p < 0.05), and reticulocyte (r = -0.447, p < 0.05). The phagocytosis of mDC does not correlate with the response to IST. CONCLUSIONS: The increased phagocytosis of mDC in untreated SAA patients may contribute to abnormal activation of T helper (Th) and subsequent cytotoxic T lymphocyte (CTL) activation in these patients. It may be involved in the immune pathogenesis of SAA.

Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia.

IL-2 is a cytokine released from CD4+T cells with dual actions and can either potentiate the inflammatory response or quell a chronic inflammatory response depending on its circulating concentration. IL-2 is elevated in many chronic inflammatory conditions and is increased during preeclampsia (PE). PE is characterized by new-onset hypertension during pregnancy and organ dysfunction and increasing evidence indicates that proinflammatory cytokines cause hypertension and mitochondrial (mt) dysfunction during pregnancy. The reduced uterine perfusion pressure (RUPP) model of placental ischemia is a rat model of PE that we commonly use in our laboratory and we have previously shown that low doses of recombinant IL-2 can decrease blood pressure in RUPP rats. The objective of this study was to determine the effects of a low dose of recombinant IL-2 on multi-organ mt dysfunction in the RUPP rat model of PE. We tested our hypothesis by infusing recombinant IL-2 (0.05 ng/mL) into RUPP rats on GD14 and examined mean arterial pressure (MAP), renal, placental and endothelial cell mt function compared to control RUPP. MAP was elevated in RUPP rats (n = 6) compared to controls (n = 5) (122 ± 5 vs. 102 ± 3 mmHg, p < 0.05), but was reduced by administration of LD recombinant IL-2 (107 ± 1 vs. 122 ± 5 mmHg, n = 9, p < 0.05). Renal, placental and endothelial mt ROS were significantly increased in RUPP rats compared to RUPP+ IL-2 and controls. Placental and renal respiration rates were reduced in RUPP rats compared to control rats but were normalized with IL-2 administration to RUPPs. These data indicate that low-dose IL-2 normalized multi-organ mt function and hypertension in response to placental ischemia.

The relationship between changes in IL-2 / IL-18 and liver enzyme with dengue severity.

A synergistic impact of virulence capacity of dengue viruses and host immune response contributes to the pathogenesis of dengue virus infection (DENV). Elevation of hepatic enzyme and cytokine storm is the major contributory factor producing severity. IL-2 and IL-18 both play a critical role in generating immunogenicity during viral infection. The goal of the study was to evaluate the correlation between alterations in IL-2 and IL-18 levels with alterations in hepatic enzymes in dengue-infected patients. Accordingly, a total of 91 NS1/IgM confirmed DENV infected patients were selected for the IL-2 and IL-18 evaluation using a standard ELISA assay. Biochemical, haematological parameters were recorded at the time of admission. Interestingly, raised levels of IL-2 (p < 0.0001) and IL-18 (p < 0.0001) was obtained in severe dengue as compared to non-severe dengue patients. A significant positive correlation was observed between IL and 2 levels and SGOT (r = 0.3168 with p = 0.002), SGPT (r = 0.569 with p < 0.0001). Similarly IL-18 was also highly associated with SGOT (r = 0.387 with p = 0.0002) and SGPT (r = 0.407 with p < 0.0001) in dengue infected patient.Our data reveal that a rising amount of IL-2 and IL-18 in initial stage of the disease could be predictors for developing severe form of dengue infection.

Molecular Biomarkers for Pediatric Depressive Disorders: A Narrative Review.

Depressive disorder in childhood and adolescence is a highly prevalent mood disorder that tends to recur throughout life. Untreated mood disorders can adversely impact a patient's quality of life and cause socioeconomic loss. Thus, an accurate diagnosis and appropriate treatment is crucial. However, until now, diagnoses and treatments were conducted according to clinical symptoms. Objective and biological validation is lacking. This may result in a poor outcome for patients with depressive disorder. Research has been conducted to identify the biomarkers that are related to depressive disorder. Cumulative evidence has revealed that certain immunologic biomarkers including brain-derived neurotrophic factor (BDNF) and cytokines, gastrointestinal biomarkers, hormones, oxidative stress, and certain hypothalamus-pituitary axis biomarkers are associated with depressive disorder. This article reviews the biomarkers related to the diagnosis and treatment of pediatric depressive disorders. To date, clinical biomarker tests are not yet available for diagnosis or for the prediction of treatment prognosis. However, cytokines such as Interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and BDNF have shown significant results in previous studies of pediatric depressive disorder. These biomarkers have the potential to be used for diagnosis, prognostic assessment, and group screening for those at high risk.

Serum Inflammatory Factor Profiles in the Pathogenesis of High-Altitude Polycythemia and Mechanisms of Acclimation to High Altitudes.

High-altitude polycythemia (HAPC) is a common aspect of chronic mountain sickness (CMS) caused by hypoxia and is the main cause of other symptoms associated with CMS. However, its pathogenesis and the mechanisms of high-altitude acclimation have not been fully elucidated. Exposure to high altitude is associated with elevated inflammatory mediators. In this study, the subjects were recruited and placed into a plain control (PC) group, plateau control (PUC) group, early HAPC (eHAPC) group, or a confirmed HAPC (cHAPC) group. Serum samples were collected, and inflammatory factors were measured by a novel antibody array methodology. The serum levels of interleukin-2 (IL-2), interleukin-3 (IL-3), and macrophage chemoattractant protein-1 (MCP-1) in the eHAPC group and the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, tumor necrosis factor-alpha (TNF-alpha), MCP-1, and interleukin-16 (IL-16) in the cHAPC group were higher than those in the PUC group. More interestingly, the expression of IL-1 beta, IL-2, IL-3, TNF-alpha, MCP-1, and IL-16 in the PUC group showed a remarkable lower value than that in the PC group. These results suggest that these six factors might be involved in the pathogenesis of HAPC as well as acclimation to high altitudes. Altered inflammatory factors might be new biomarkers for HAPC and for high-altitude acclimation.

Effect of Chaihu-jia-Longgu-Muli decoction on withdrawal symptoms in rats with methamphetamine-induced conditioned place preference.

Traditional Chinese medicine detoxification prescription Chaihu-jia-Longgu-Muli decoction (CLMD) relieves depressive symptoms in patients withdrawing from methamphetamine. In the present study, we assessed the effects of CLMD on methamphetamine withdrawal in rats. A methamphetamine-intoxicated rat model was established. Rats were randomly divided into the control, model, high-dosage, medium-dosage, and low-dosage groups, receiving high, medium, and low doses of CLMD, respectively. Weekly body weight measurements revealed that rats treated with methamphetamine had the lowest body weight. The conditioned place preference (CPP) experiment revealed that methamphetamine-intoxicated rats stayed significantly longer in the drug-paired chamber than the control rats. However, after administering high-dosage CLMD, the amount of time the rats spent in the drug-paired chamber was significantly less than that of the model rats. Our open-field test revealed that the model group had lower crossing and rearing scores than the control group. Additionally, rats that received CLMD treatment exhibited higher crossing and rearing scores than the model rats. Striatal dopamine (DA), 5-hydroxytryptamine (5-HT), and endorphins (ß-EP) and serum interleukin (IL)-1α and IL-2 concentrations were estimated. Rats in the model group had lower striatal DA, 5-HT, and ß-EP and higher serum IL-1α and IL-2 concentrations than those in the control group. High-dosage CLMD administration significantly changed the concentrations of these molecules, such that they approached normal concentrations. In general, CLMD could prevent the development of methamphetamine-induced withdrawal symptoms in rats by increasing the DA, 5-HT, and ß-EP and lowering the IL-1α and IL-2 concentrations.

Peripheral blood and tissue assessment highlights differential tumor-circulatory gradients of IL2 and MIF with prognostic significance in resectable pancreatic ductal adenocarcinoma.

Various reports have pointed out the potential of cytokines as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDA). Nonetheless, the evidence is contradictory and the role of chronic inflammation and relationship between circulatory and corresponding tumoral cytokine levels remain elusive. Utilizing a broad array of cytokines, we identified two opposing parameters: serum levels of interleukin 2 (IL2) and macrophage migration inhibitory factor (MIF) are diagnostic and prognostic factors. While low IL2 levels are associated with PDA, they also relate to a favorable prognosis of patients. In contrast, high MIF levels are associated with PDA and simultaneously related to an unfavorable outcome. MIF levels are associated with the intratumoral density of M2 macrophages (CD163+). Focusing on the tumor-to-serum gradient, we unveiled a different pattern of compartmental cytokine expression between IL2 and MIF. Our findings indicate that an extra-tumoral source of IL2 exists in PDA patients leading to increased detectability in the circulatory system. In case of MIF, the tumor microenvironment is presumably the main site of production and thereby reflected by serum measurements. Taken together, our study describes IL2 and MIF levels as biomarker candidates for diagnosis and prognosis of PDA, highlighting the need for compartmental cytokine analyses. From the perspective of tumor immunobiology, we identify multiple inflammatory states (proposed as types I-III) and see that systemic chronic dysregulation, independent of tumor microenvironment, can be measured and is a possible tool for stratification. Thus, direct correlation of local cytokine levels to peripheral blood levels needs to be regarded with caution.

Cytokine Imprint in Preeclampsia.

The hallmark of preeclampsia (PE) is a shift toward persistent inflammatory response, accompanied by endothelial dysfunction. The driving forces in PE are proinflammatory cytokine and growth factors, in parallel with reduced functionality of anti-inflammatory effectors, like regulatory T cells are observed. Unfortunately, no conclusive mechanism underlying preeclampsia has been identified. For this reason, research on preeclampsia is needed to provide a state of the art understanding of the pathophysiology, identification of new diagnostics tools and the development of targeted therapies. The 68 patients were divided into three groups: gestational hypertension (GH) group (n = 19) and PE group (n = 28) and a control group (n = 21). We have tested a set of 53 cytokines, chemokines and growth factors in preeclampsia and gestational hypertension, and then compared them with normal pregnancies. Using a diagnostic test assessment characteristic parameters (IL-22, MDC/CCL22, IL-2/IL-4 ratio) have been identified and cut-off values have been proposed to diagnose preeclampsia. All parameters had high negative or positive predictive values, above 80%. In conclusion, we have proposed a potential set of immune parameters to diagnose preeclampsia.

New Tool for Rapid and Accurate Detection of Interleukin-2 and Soluble Interleukin-2 Receptor α in Cancer Diagnosis Using a Bioresponsive Microgel and Multivalent Protein Binding.

Interleukin-2 (IL-2) and its α receptor in soluble form (sIL-2Rα) are considered biomarkers for cancers and immune-related diseases. Enzyme-linked immunosorbent assay is the most common method used to evaluate biomarkers in clinical practice; it is precise but time-consuming and involves complicated procedures. Here, we have developed a rapid yet accurate modality for cancer diagnosis that enables on-site evaluation of cancer markers, that is, IL-2 and sIL-2Rα, without complicated pretreatment of cancer patient-derived blood samples. Surface plasmon resonance and bioresponsive microgels conjugated with IL-2 receptors, that is, IL-2Rß and IL-2Rγ, were utilized to measure IL-2 and sIL-2Rα levels via multivalent protein binding (MPB) between the ligands and their receptors. Our results showed that this novel method enables us to perform cancer diagnosis with a 1000-fold dilution of serum in 10 min. The advantage of MPB-based cancer diagnosis originates from its great selectivity for a target molecule and tolerance to a myriad of nonspecific substances in serum, which allows on-site clinical evaluation. Importantly, our finding implies that MPB-based cancer diagnosis provides a new paradigm not only for improving cancer treatment but also for evaluating a target molecule in unpurified and complex solutions such as blood.

Association of interleukin-2, interleukin-21 and interleukin-23 with hyperlipidemia in pediatric type 1 diabetes.

BACKGROUND: In type 1 diabetes mellitus (T1DM), cytokines have a central role in orchestrating multicellular relations between ß-cells and immune cells. This study aims to investigate the role of interleukin (IL)-21, IL-23, and IL-2, and their association with dyslipidemia in T1DM children. METHODS: The sample population consisted of 30 healthy controls and 70 children with T1DM, the latter of which were split into two groups according to the duration of their T1DM diagnosis: recent (≤ 1 year; n = 21) and older (> 1 year; n = 49) diagnoses. RESULTS: Fasting blood sugar and glycated hemoglobin levels in all diabetic children were significantly (P < 0.001) higher, whereas levels of plasma C-peptide were markedly (P < 0.001) lower in children with T1DM compared to healthy controls. In older T1DM diagnosis children, the levels of creatinine were noticeably (P < 0.05) increased relative to healthy controls. In all diabetic children, levels of total triglyceride, cholesterol, and low-density lipoprotein were increased significantly (P < 0.001) than those of healthy controls. Furthermore, the IL-21 and IL-23 mRNA expressions of all children with T1DM were elevated significantly (P < 0.001) relative to healthy controls, whereas IL-2 levels revealed a significant (P < 0.001) decrease in all diabetic children. CONCLUSION: There was a synergistic interplay between IL-21 and IL-23 with an antagonistic action of IL-2 in T1DM patients, and all three interleukins were associated with dyslipidemia in diabetic children. Importantly, therapies targeting IL-21 and IL-23 are promising targets for preventive strategies against the development of T1DM and its complications.