IFN-γ In Patients Research Articles

Levels of cytokines in the cerebrospinal fluid of patients with psychotic disorders compared to individually matched healthy controls

BackgroundIncreased peripheral cytokine levels have been observed in patients with psychotic disorders; however, large high-quality studies with individually matched healthy controls have been lacking regarding cytokines in cerebrospinal fluid (CSF) of individuals with psychotic disorders. MethodsPatients diagnosed with a non-organic, non-affective psychotic disorder (ICD-10: F20/22–29) within a year prior to inclusion and individually age- and sex-matched healthy controls were included by identical in- and exclusion criteria’s except for the psychiatric diagnoses. All participants were aged 18–50 years and individuals with neurological or immunological disorders were excluded. CSF cytokines were analyzed with MesoScale V-PLEX neuroinflammation panel. Co-primary outcomes were CSF interleukin-6 (IL-6) and IL-8. ResultsWe included 104 patients and 104 healthy controls, matching on age, sex and BMI. No significant differences were found for the primary outcomes IL-6 (relative mean difference (MD): 0.97, 95 %CI: 0.84–1.11, p = 0.637) or IL-8 (MD: 1.01, 95 %CI: 0.93–1.09, p = 0.895). Secondary analyses found patients to have higher IL-4 (MD: 1.30, 95 %CI: 1.04–1.61, p = 0.018), a trend towards higher IFN-γ (MD: 1.26, 95 %CI: 0.99–1.59, p = 0.056), and lower IL-16 (MD: 0.83, 95 %CI: 0.74–0.94, p = 0.004) than healthy controls, though not significant after correction for multiple testing. IL-8 and IL-16 were found positively associated with CSF white blood cells and CSF/serum albumin ratio. The study was limited by 77.9 % of the patients being on antipsychotic treatment at time of intervention, and that levels of nine of the 26 cytokines were below lower limit of detection (LLOD) in >50 % of samples; however, for the primary outcomes IL-6 and IL-8 more than 99.5 % of the samples were above LLOD and for IL-8 all samples exceeded the lower limit of quantification (LLOQ). ConclusionsWe found no evidence of increased IL-6 and IL-8 in patients with recent-onset psychotic disorders in contrary to previous findings in meta-analyses of CSF cytokines. Secondary analyses found indication of higher IL-4, decreased IL-16, and borderline increased IFN-γ in patients, neither of which have previously been reported on in CSF analyses of individuals with psychotic disorders.

Interleukin-17 and interferon-gamma in patients with different forms of non-ischemic cardiomyopathies

Abstract Introduction Dilated cardiomyopathy (DCM) characterized by left ventricular dilation and impaired left ventricular function represents a common and severe cause of heart failure (HF). Predominantly affecting younger patients, it is considered a leading cause for sudden cardiac death and heart transplantation. Several studies identified myocarditis as a substantive precursor and potential cause of DCM. Inflammatory cardiomyopathy (DCMi) can lead to cardiomyocytal damage and exposure of cardiac myosin and other heart proteins. This cascade can in susceptible individuals trigger an altered immune response consecutively leading to autoimmunity and chronic inflammation. A variety of inflammatory and immunologic agents are discussed to be involved in the pathophysiology of myocardial inflammation. Several studies suggested a role of Interleukin -17 (IL-17) and Interferon-γ (IFN-γ) in chronic HF, myocardial infarction and other cardiovascular diseases. Underlying pathomechanisms, however, are poorly understood. Methods In this study we measured IL-17 and IFN-γ levels in serum by ELISA in patients in which an endomyocardial biopsy (EMB) was performed due to chronic unexplained heart failure symptoms after exclusion of ischemic or valvular heart disease at our center. All patients underwent transthoracic echocardiography prior to EMB sampling. Patients were classified according to the histological presence of inflammation into DCMi, DCM and patients with preserved left ventricular ejection fraction (LVEF) without inflammation. EMB specimens were analyzed including histology, immunohistochemistry and molecular virology. Results A total of 289 patients were included into the final analysis. Mean age was 47 years and 71% were male. Mean LVEF was 50% and mean left ventricular end-diastolic diameter (LVEDD) was 57 mm. Based on EMB results, 71 (25%) samples were categorized as DCMi and 113 (39%) as DCM. 105 (36%) samples were assigned to the group without myocardial inflammation and normal LVEF. The groups differed significantly in their inflammatory profiles. Levels of IL-17 (p < 0.001) and IFN-γ (p < 0.01) were significantly higher in patients with DCMi compared to the DCM as well as the normal LVEF group (Figure 1, Figure 2). Therefore, this effect is not specific for heart failure, but seems to be an important mediator in inflammatory cardiomyopathy. Conclusion Our data showed a significant elevation of IL-17 and IFN-γ in patients with inflammatory dilated cardiomyopathy. These findings suggest that these agents play an important role in the disease entity development and progression that remains poorly understood. So far treatment strategies in DCMi are unspecific. Therefore, blocking IL-17 expression could be an interesting potential therapeutic target in future (personalized) treatment for a wide group of patients with heart failure generated by inflammatory causes.Serum IL-17 levels.t-SNE analysis of the different groups.

Plasma levels of 12 different cytokines correlate to PD-1 inhibitor combined chemotherapy responses in advanced non-small-cell lung cancer patient

BackgroundTargeted anti-programmed death receptor 1 (PD-1) monoclonal antibodies, when combined with chemotherapy, have shown improved outcomes in non-small cell lung cancer (NSCLC). However, it is important to note that not all patients benefit from this treatment, and there is a pressing need for more reliable efficacy measures and potential predictors of outcome. Cytokines, which are important molecules in the immune system, have been considered as potential biomarkers in clinical settings, but their precise clinical use remains unclear. In this study, our objective was to assess whether the levels of cytokines in the patient's blood sample are associated with tumor response to anti-PD-1 monoclonal antibodies combined with chemotherapy as well as the survival of patients with advanced non-small cell lung cancer. Materials and MethodsA total of 12 plasma cytokines were measured in advanced NSCLC patients (n = 35) and healthy individuals (n = 26) using multi-microsphere flow immunofluorescence. The relationship between cytokine levels and clinical response was analyzed using nonparametric Wilcoxon matched-pair ranked tests. Progression-free survival (PFS) time was recorded for all patients through radiographic outcome assessment and telephone follow-up. Survival curves were generated using the Kaplan-Meier and log-rank tests, and the thresholds for cytokines were determined using receiver operating characteristic analysis (ROC). ResultsThe expression levels of interleukin IL-6, IL-1 β, IFN-γ, IL-12p70, and TNF-α were significantly lower in the control group than those in the NSCLC group (p = 0.001, p = 0.0028, p = 0.019, p = 0.0001, p = 0.0021). High IL-10 levels at baseline and after 4 cycles of treatment conferred a worse prognosis; in addition, high TNF-α levels in patients after two cycles of immunochemotherapy suggested drug resistance. High levels of IL-6 and IFN-γ in patients undergoing four cycles of immunochemotherapy were associated with worse PFS. ConclusionsOur study suggests that cytokines can serve as detection indicators for predicting efficacy in non-small cell lung cancer patients undergoing anti-PD-1 combined with chemotherapy treatment. Elevated levels of IL-10, TNF-α, IL-6, and IFN-γ in the plasma may indicate a higher likelihood of experiencing a worse clinical outcome.

Neutrophils exacerbate acetaminophen-induced liver injury by producing cytotoxic interferon-γ

BackgroundDrug (e.g., acetaminophen, APAP)-associated hepatotoxicity is the major cause of acute liver failure. Emerging evidence shows that initial tissue damage caused by APAP triggers molecular and cellular immune responses, which can modulate the severity of hepatoxicity. The pro-inflammatory and cytotoxic cytokine interferon (IFN)-γ has been reported as a key molecule contributing to APAP-induced liver injury (AILI). However, its cellular source remains undetermined. ResultsIn the current study, we show that elevation of serum IFN-γ in patients with drug hepatotoxicity correlates with disease severity. Neutralization of IFN-γ in a mouse model of AILI effectively reduces hepatotoxicity. Strikingly, we reveal that IFN-γ is expressed primarily by hepatic neutrophils, not by conventional immune cells with known IFN-γ-producing capability, e.g., CD8+ T cells, CD4+ T cells, natural killer cells, or natural killer T cells. Upon encountering APAP-injured hepatocytes, neutrophils secrete cytotoxic IFN-γ further causing cell stress and damage, which can be abrogated in the presence of blocking antibodies for IFN-γ or IFN-γreceptor. Furthermore, removal of neutrophils in vivo substantially decreases hepatic IFN-γ levels concomitantly with reduced APAP hepatotoxicity, whereas adoptive transfer of IFN-γ-producing neutrophils confers IFN-γ-/- mice susceptibility to APAP administration. ConclusionsOur findings uncover a novel mechanism of neutrophil action in promoting AILI and provide new insights into immune modulation of the disease pathogenesis.

Characterization of TIM-3 Expression and Its Correlation with TNF-α and IFN-γ in Patients with Surgically Resected Lung Adenocarcinoma.

T cell immunoglobulin and mucin-containing protein-3 (TIM-3) is an important immune checkpoint, but its role in lung cancer is still not clear. In this study, we investigated TIM-3 protein expression and its correlation with TNF-α and IFN-γ by examining the tissues of patients with lung adenocarcinoma. We detected the mRNA quantity of TIM-3, TNF-α, and IFN-γ in 40 surgically resected specimens from patients with lung adenocarcinoma by real-time quantitative polymerase chain reaction (qRT-PCR). The protein expression of TIM-3, TNF-α, and IFN-γ was assessed in normal tissues, paracarcinoma tissues, and tumor tissues by western blotting, respectively. The relevance between the expression and clinicopathological information of the patients was analyzed. The results showed that the expression level of TIM-3 was higher in tumor tissues than normal tissues and paracancerous tissues (P < 0.05). On the contrary, the expression of TNF-α and IFN-γ in tumor tissues was lower than normal tissues and paracarcinoma tissues (P < 0.05). However, the expression levels of IFN-γ mRNA were not observed to be significantly different between cancerous tissues and adjacent tissues. While TIM-3 protein expression in cancer tissues of patients with lymph node metastasis was higher than in patients without metastasis, the expression of TNF-α and IFN-γ was lower (P < 0.05). Importantly, the expression of TIM-3 was negatively correlated with the expression of TNF-α and IFN-γ, and the expression of TNF-α was found to be positively correlated with IFN-γ in the patient. The high expression of TIM-3, the low expression of TNF-α and IFN-γ, and the synergistic effect of TNF-α and IFN-γ in patients with lung adenocarcinoma were closely related to poor clinicopathological characteristics. Overexpression of TIM-3 may play an important role in the relationship between TNF-α and IFN-γ secretion and poor clinicopathological characteristics.

Regulation of Cytotoxic Immune Effector Function by AJ3 Probiotic Bacteria in Amyotrophic Lateral Sclerosis (ALS).

Our recent studies indicated that amyotrophic lateral sclerosis (ALS) patients suffer from significantly elevated levels of interferon-gamma (IFN-γ) secretion by natural killer (NK) and CD8+ T cells, which may be responsible for the immune-pathologies seen in central nervous system and in peripheral organs of the patients. In order to counter such elevated induction of IFN-γ in patients we designed a treatment strategy to increase anti-inflammatory cytokine interleukin-10 (IL-10) by the use of probiotic strains which significantly increase the levels of IL-10. Therefore, in this paper we demonstrate disease specific functions of Al-Pro (AJ3) formulated for the adjunct treatment of auto-immune diseases including ALS, and compared the function with CA/I-Pro (AJ4) for the treatment of cancer and viral diseases, and NK-CLK (AJ2) for maintenance of immune balance and promotion of disease prevention. The three different formulations of probiotic bacteria have distinct profiles of activation of peripheral blood mononuclear cells (PBMCs), NK, and CD8+ T cells, and their induced activation is different from those mediated by either IL-2 or IL-2 + anti-CD16 monoclonal antibodies (mAbs) or IL-2 + anti-CD3/CD28 mAbs. IL-2 + anti-CD16 mAb activation of PBMCs and NK cells had the highest IFN-γ/IL-10 ratio, whereas IL-2 combination with sAJ4 had the next highest followed by IL-2 + sAJ2 and the lowest was seen with IL-2 + sAJ3. Accordingly, the highest secretion of IFN-γ was seen when the PBMCs and NK cells were treated with IL-2 + sAJ4, intermediate for IL-2 + sAJ2 and the lowest with IL-2 + sAJ3. The levels of IFN-γ induction and the ratio of IFN-γ to IL-10 induced by different probiotic bacteria formulation in the absence of IL-2 treatment remained much lower when compared to those treated in the presence of IL-2. Of note is the difference between NK cells and CD8+ T cells in which synergistic induction of IFN-y by IL-2 + sAJ4 was significantly higher in NK cells than those seen by CD8+ T cells. Based on these results, sAJ3 should be effective in alleviating auto-immunity seen in ALS since it will greatly regulate the levels and function of IFN-γ negatively, decreasing overactivation of cytotoxic immune effectors and prevention of death in motor neurons.

Time-dependent dual beneficial modulation of interferon-γ, interleukin 5, and Treg cytokines in asthma patient peripheral blood mononuclear cells by ganoderic acid B.

Th2 cytokines play a dominant role in the pathogenesis of allergic asthma. Interferon gamma (IFN-γ), a Th1 cytokine, links to therapeutic mechanisms of allergic asthma. Interleukin (IL)-10, a regulatory cytokine, is involved in the induction of immune tolerance. We previously demonstrated that Anti-Asthma Simplified Herbal Medicine Intervention (ASHMI) suppressed Th2 and increased IFN-γ in patients with asthma and in animal models, but its bioactive compound is unknown. Ganoderic acid beta (GAB) was isolated from Ganoderma lucidum (one herb in ASHMI). Human peripheral blood mononuclear cells (PBMCs) from adult patients with asthma were cultured with GAB or dexamethasone (Dex) in the presence of environmental allergens. The cytokine levels of IL-10, IFN-γ, IL-5, transcription factors T-bet, Foxp-3, and GATA3 were measured. Following 3-day culture, GAB, but not Dex, significantly increased IL-10 and IFN-γ levels by allergic patients' PBMCs. Following 6-day treatment, GAB inhibited IL-5 production, but IL-10 and IFN-γ remained high. Dex suppressed production of all three cytokines. GAB suppressed GATA3 and maintained Foxp-3 and T-bet gene expression, while Dex significantly suppressed GATA3 and T-bet expression. GAB simultaneously increased IL-10, IFN-γ associated with induction of T-bet and Foxp3, while suppressing IL-5, which was associated with suppression of GATA3, demonstrating unique beneficial cytokine modulatory effect, which distinguishes from Dex's overall suppression.

Changes of Host Immunity Mediated by IFN-γ+ CD8+ T Cells in Children with Adenovirus Pneumonia in Different Severity of Illness.

The host immunity of patients with adenovirus pneumonia in different severity of illness is unclear. This study compared the routine laboratory tests and the host immunity of human adenovirus (HAdV) patients with different severity of illness. A co-cultured cell model in vitro was established to verify the T cell response in vitro. Among 140 patients with confirmed HAdV of varying severity, the number of lymphocytes in the severe patients was significantly reduced to 1.91 × 109/L compared with the healthy control (3.92 × 109/L) and the mild patients (4.27 × 109/L). The levels of IL-6, IL-10, and IFN-γ in patients with adenovirus pneumonia were significantly elevated with the severity of the disease. Compared with the healthy control (20.82%) and the stable patients (33.96%), the percentage of CD8+ T cells that produced IFN-γ increased to 56.27% in the progressing patients. Adenovirus infection increased the percentage of CD8+ T and CD4+ T cells that produce IFN-γ in the co-culture system. The hyperfunction of IFN-γ+ CD8+ T cells might be related to the severity of adenovirus infection. The in vitro co-culture cell model could also provide a usable cellular model for subsequent experiments.

Faster speed of onset of the depressive episode is associated with lower cytokine serum levels (IL-2, -4, -6, -10, TNF-α and IFN-γ) in patients with major depression

IntroductionCytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels. MethodSerum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview. ResultsWe found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6–24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode. ConclusionsPatients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.

Исследование иммунопатологических процессов, связанных с развитием фиброза печени

The aim of this study was to determine the dependence of the course of liver fibrosis on the functional state of the immune system, in particular, on the imbalance of pro-inflammatory and anti-inflammatory immune reactions that are formed in patients during the development of the disease. The study included 30 patients with chronic liver diseases (18 patients with chronic hepatitis C (CHC) and 12 patients with alcoholic liver disease (ALD), 15 healthy individuals were the comparison group. Liver elastography (FibroScan) was used to evaluate liver stiffness and determine fibrosis stages according to METAVIR classification. The following cytokine levels were measured in the serum samples of the group: IL-1β, TNF-α, IL-6, IFN-γ, IL-2, IL-4, IL-8, VEGF and TGF-β. According to the data presented in this work, in patients with CHC and ALD, there was a statistically significant increase in serum levels of pro-inflammatory cytokines, namely: IL-1β, TNF-α, IFN-γ, IL-2, IL-6 and IL-8. Interestingly, elevated TGF-β values were found in patients with CHC, but not in patients with ALD. Significantly lower concentrations of VEGF were observed in both study groups. There was also a significant decrease in serum IL-4 in patients with CHC, whereas in patients with ALD such a decrease was not statistically significant. Serum IL-1β content was approximately equally elevated in the early and late stages of fibrosis. A sharp rise in serum TNF-α levels occurred in the early stages of fibrosis. In the later stages, the rise in the level was replaced by a sharp fall. However, the serum levels of TNF-α in the later stages of liver fibrosis still significantly exceeded control values. The serum levels of IFN-γ in patients significantly exceeded control values without changes in different stages of fibrosis. Relatively high levels of serum IL-2 and IL-6 were noted only in the later stages of the disease. In both groups of patients, a clear dependence of serum levels of IL-8 on the stage of fibrosis was revealed. Analysis of the data allows us to conclude that immune mechanisms play a significant role in the pathogenesis of degenerative liver diseases. Therefore further studies of the mechanism and role of immune factors is required to explore possible diagnostic and therapeutic applications.

Interferon gamma in the treatment of patients with moderate COVID-19

Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.

Analysis of systemic cytokine levels in silicosis complicated with pulmonary infection

Objective: To investigate the changes of cytokine profile in elderly patients with silicosis and lower respiratory tract infection and its clinical significance. Methods: In Oclober 2019, a retrospective study was conducted to select 167 elderly patients with silicosis from Xuzhou Mining Group General Hospital as subjects, including 115 patients with silicosis and lower respiratory tract infection as infected group, including 41 patients with stage I silicosis, 38 patients with stage II silicosis and 36 patients with stage III silicosis. There were 52 cases of silicosis without lower respiratory tract infection as non-infected group, and 48 cases of healthy examination in our hospital were selected as control group. All the participants were tested for cytokines (IL-6, IL-10, IL-17A, TNF-α, IFN-γ) and statistically analyzed the relevant experimental data. Results: The levels of IL-6, IL-10, IL-17A, TNF-α and IFN-γ in the infected group after treatment were significantly lower than those before treatment (P<0.05) . The levels of IL-6, IL-10, IL-17A, TNF-α and IFN-γ before and after treatment in the infected group were higher than those in the non-infected group and the control group (P<0.05) . The levels of IL-10, IL-17A, TNF-α and IFN-γ in the infected group were higher than those in the control group, and the difference were statistically significant (P<0.05) . The levels of IL-6, IL-10, IL-17A and IFN-γ in patients with stage III silicosis were higher than those in stage I silicosis in infected group (P<0.05) . The levels of IL-6 and IL-17A in the patients with stage Ⅲ silicosis were higher than those in the patients with stage II silicosis in infected group (P<0.05) . The level of IL-10 in patients with stage II silicosis was higher than that in stage I in infected group (P<0.05) . ROC curve analysis of the indicators for diagnosis of senile silicosis with lower respiratory tract infection and silicosis without lower respiratory tract infection found that IL-6 had the largest AUC (0.910) . And its specifuity and sensithcity were 85.2% and 98.1% respectivehy. Conclusion: The detection of cytokines such as IL-6 and IL-10 has better specificity and higher diagnostic efficiency in the early diagnosis and treatment of elderly patients with silicosis complicated with lower respiratory tract infection. It has good clinical application value and can provide important laboratory evidence for early treatment for clinicians.

Evaluation of immunological role of Interferon gamma, Interleukin-10 and CD4+ T lymphocytes in pediatric patients with sickle cell disease

Sickle cell disease (SCD) is a chronic inflammatory disease associated with increased levels of multiple cytokines as interferon gamma (IFN-γ) during vaso-occlusive (VOC) crisis and steady state. Therefore, we aimed to explore theimmunological role of serum IFN-γ, interleukin-10 (IL-10) and CD4+ T lymphocytes in children with SCD at steady state and VOC. This study was conducted on 30 children with SCD (15 at steady state and 15 in VOC) and 30 healthy children as controls. Detailed history, complete physical, clinical examination and laboratory investigations as: complete blood count, serum ferritin, IFN-γ, IL-10 and CD4+ T lymphocytes for all patients were recorded. Results: Significant increase in serum IFN-γ in patients with SCD during VOC compared with patients at steady state and controls (P<0.001). Significant increase in serum IL-10 in patients with SCD at steady state compared with those during VOC and controls (P=0.008 and P=0.04 respectively). CD4 +T lymphocyte decreased in patients with SCD during VOC compared with those at steady state and controls (P<0.001). There was a significant positive correlation between serum IFN-ɣ and number of crisis per year (r=0.648, P=0.0001). Serum IFN-γ was increased in patients with history of frequent crisis per year (P=0.001) and decreased in patients under hydroxyurea therapy (P<0.001). IFN-γ was increased in SCD patients. Increased IFN-γ production in SCD suggesting that functionally activated natural killer cells reflecting a host immunological mechanism leading to antigen antibody activation in SCD. Serum IL-10 increased in SCD patients at steady state. CD4 +T lymphocyte decreased in patients during VOC.

Cytokine profile and disease severity in patients with COVID-19

Cytokine dysregulation is the proposed mechanism for Coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the serum levels of interferon (IFN)-γ, interleukin (IL)-5, IL-8, Il-9, IL-17, TGF-β and IFN-γ in patients infected with SARS-CoV-2. The study was conducted between 63 adult patients with COVID‐19 and compared with 33 age and gender-matched healthy subjects as controls. The age range in both groups was 50–70 years. The patients were classified into mild group (33 patients) and severe group (30 patients). Serum samples were collected from all participants and tested for the cytokine levels by ELISA (enzyme-linked immunosorbent assay) method. Statistical analysis was performed using the one-way ANOVA. The mean serum levels of IFN-γ, TGF-β, IL-17 and IL-8 in the COVID‐19 patients were significantly higher than those observed in the control group. A comparison of between the mild and severe groups showed significant differences in TGF-β levels. The mean concentration of serum IL-5 and IL-9 in patients with COVID‐19 did not differ from those in the control group. Systemic IL-17 levels correlated positively and significantly with TGF-β in patients with COVID‐19. Th1 (IFN-γ), Treg (TGF-β), and Th17 (IL-17) cytokines concentration were increased in COVID-19 patients. Interferon-γ and IL-17 are involved in inducing and mediating proinflammatory responses. Our data suggest that TGF-β can be used as a predictive factor of disease severity in patients with COVID-19.

Postoperative psychological stress and expression of stress-related factors HSP70 and IFN-γ in patients with early lung cancer.

To explore the status of postoperative psychological stress and the expression of stress-related factors heat stress protein 70 (HSP70) and interferon γ (IFN-γ) in patients with early lung cancer, and to provide scientific basis for psychological rehabilitation and index detection of patients with lung cancer. Patients with early lung cancer hospitalized in People's Hospital of Rizhao from April 2014 to March 2017 were selected as the research subjects, and a cross-sectional survey research method was used to conduct a questionnaire survey on the research subjects. The questionnaire included General Data Questionnaire and the SCL-90 Self-Assessment Scale for Health Symptoms, which were used to research the postoperative psychological stress of patients with early lung cancer. The enzyme-linked immunosorbent assay was used to detect the serum levels of HSP70 and IFN-γ. A total of 178 patients with early lung cancer were investigated, including 126 males (70.8%) and 52 females (29.2%). There were 52.6% of the patients with mild discomfort, 29.9% with moderate discomfort and 4.8% with severe discomfort, and the positive detection rate of psychological problems was 44.2%. The SCL-90 factors of the patients were higher than the norm, and the average scores of factors including anxiety, horror, somatization, depression, and interpersonal sensitivity were higher (P<0.05). Serum HSP70 expression level was the highest in patients with moderate discomfort of early lung cancer (P<0.05), and the serum IFN-γ expression level decreased with the increased stress level (P<0.05). HSP70 was positively correlated with somatization factors, and negatively correlated with fear factors, and IFN-γ was negatively correlated with the fear factor. Patients with early lung cancer have extensive postoperative psychological problems, and the timely postoperative psychological intervention is significant. There are differences in the expression levels of stress related factors HSP70 and IFN-γ in patients with different levels of psychological stress, which are of certain clinical value as the monitoring index of response psychological stress.

Dectection of Erythrocyte Life and Analysis of Its Effect on the Anemia in Patients with Hemophagocytic Syndrome

To detect the erythrocyte life by breath carbon monoxide assay and to analyze the effect of erythrocyte life on the anemia in patients with hemophagocytic syndrome. The breath carbon monoxide test and erythrocyte life assay were performed for 20 cases of hemophagocytic syndrome, at the same time the detection of 20 healthy persons was used as control. The difference of anemia-related indexes was compared between hemophagocytic syndrome patients and healthy persons. The average erythrocyte life of patients with hemophagocytic syndrome was 45.3 days, which was 65% shorter than that of healthy persons. Hemoglobin levels positively correlated with erythrocyte life, while sCD25, breath carbon monoxide concentration and hemophagocytosis negatively correlated with erythrocyte life. Bilirubin level and reticulocyte count showed no correlation with erythrocyte life. Serum level of IL-1β, IL-2, sCD25, IL-6, IL-10, IL-17A, GM-CSF, TNF-α and IFN-γ in patients with newly diagnosed hemophagocytic syndrome were significantly higher than those of healthy persons (P＜0.05). Breath carbon monoxide assay is a rapid and efficient method to assess erythrocyte life. Increased erythrocyte destruction may be an important pathogenic factor for anemia in hemophagocytic syndrome.

Estimation of Interferon Gamma and Zinc Concentration in Serum of Cutaneous Leishmaniasis Patients in Tikrit City

Background: Interferon-gamma is one of the important cytokines, that has a role in the immune system of the body. Also zinc has optimal activity on the immune system and is involved in cell and tissue growth. The aim of this study is to evaluate IFN-γ and Zn concentration in the serum of CL patients and compare to control groups. Patients and Method: A total of 96 persons were included in this study, during the period from January/2018 to the end of June/2018 in the outpatients of Dermatology Department of Tikrit Teaching Hospital. Forty eight patients with CL were included in this study, 43.75% were males and 56.25% were females. Assessment of zinc concentration by using spectrophotometer, so interferon gamma by ELISA. Results: There was low serum zinc in CL patients comparing to control, since mean zinc concentration in patients was 9.6 μmol/I and in control was 11.4 μmol/l. Also this study revealed that there was decrease serum zinc in CL patients in contrast to control groups aged &gt;15 years old, since mean zinc concentration in patients was 9.7 μmol/l while in control was 10.9 μmol/l. Mean zinc concentration in male patients and control were (10.0 and 11.6) μmol/l respectively. Mean zinc concentration in female patients (9.4) μmol/l while in female control is higher (10.8) μmol/l. mean serum interferon gamma is significant increase in serum patients (P&lt;0.01) than control groups aged &lt; 15 old. Since mean of IFN-γ was 0.8 IU/ml in patients and 0.5 IU/ml in control. Also serum IFN-γ in patients and control groups (aged &gt; 15 years old) were (1.0 and 0.6) IU/ml respectively. In addition to that it was found that there is significant increase in IFN-γ concentration (P &lt;0.01) in male patients which was (1.1) IU/ml in comparison with the male control which was (0.6) IU/ml. Also the same thing is noticed in females. Mean IFN-γ in female patients and control were (0.7 l and 0.5) IU/ml Respectively.

Effect of acupuncture on the expressions of TNF-α and IFN-γ in patients with premature ovarian failure

To explore the clinical effect of acupuncture and the potential effect mechanism in patients with premature ovarian failure. A total of 104 patients with premature ovarian failure were randomized into an acupuncture group and a western medication group, 52 cases in each one. In the western medication group, the conjugated estrogens tablets were prescribed for oral administration, 0.625 mg each time, once a day, consecutively for 21 days. On the 16th day of medication with conjugated estrogens tablets, the oral administration of medroxyprogesterone acetate tablets were supplemented, 10 mg each time, once a day, consecutively for 5 days, and then, these two kinds of western medication were discontinued for 1 week. A total of 3 cycles were required in treatment with 28 days as an artificial cycle. In the acupuncture group, acupuncture was applied. Two groups of acupoints were selected. The first group of acupoints were stimulated before ovulation and the acupoints were Guanyuan (CV 4), Guilai (ST 29), Taichong (LR 3), Taixi (KI 3), Xuehai (SP 10), Sanyinjiao (SP 6), Zigong (EX-CA 1), Yinlingquan (SP 9), Zusanli (ST 36), Shuidao (ST 28), Dahe (KI 12) and Tianshu (ST 25). The second group of acupoints were stimulated after ovulation and the acupoints included Ciliao (BL 32), Shiqizhui (EX-B 8), Ganshu (BL 18), Shenshu (BL 23), Geshu (BL 17) and Pishu (BL 20). The therapeutic effect was observed and compared in the patients between the two groups, as well as the expressions of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) and the levels of serum luteinizing hormone (LH), follicule stimulating hormone (FSH) and estradiol (E2) before and after treatment. The total effective rate was 90.4% (47/52) in the acupuncture group, higher than 67.3% (35/62) in the western medication group (P<0.05). After treatment, the expressions of IFN-γ and TNF-α in the acupuncture group were obviously lower than the western medication group (P<0.05). Except for serum LH after treatment, at the end of treatment and in 30 days and 90 days after treatment, the levels of serum E2 in the acupuncture group were higher obviously than the western medication group and the levels of serum LH and FSH were lower obviously than the western medication group (all P<0.05). Acupuncture promotes the regular menstruation, effectively regulates the levels of serum LH, FSH and E2 and improves the pituitary gland and the ovary endocrine in the patients with premature ovarian failure. Such effect may be related to the the improvements in the expressions of IFN-γ and TNF-α, the inhibition of the apoptosis of ovarian granulosa cells, the recovery of ovarian function and the enhancement of reserve capacity.

Treatment of type 1 diabetes by regulatory T-cell infusion via regulating the expression of inflammatory cytokines.

To explore the role and molecular mechanism of regulatory T (Treg) cells in type 1 diabetes (T1D). Patients with T1D and the healthy volunteers were selected and a number of CD3+ , CD4+ , CD25+ , and CD127- T cells were determined. The rats were divided into the control, T1D model, and Treg infusion (T1D rats were infused with Treg) group. The number of CD4+ , CD8- , and CD25+ T cells in the three groups were determined by flow cytometry. Weight, blood glucose, serum insulin, peptide C, glucagon, and glucagon like peptide 1 in the three groups were also determined. The messenger RNA (mRNA) levels and contents of interleukin (IL)-10, IL-4, transforming growth factor (TGF)-β, IL-2, IL-17, and IFN-γ in patients with T1D, healthy volunteers, streptozotocin (STZ)-induced T1D rat model, the control rat, and Treg infusion rats were determined by reverse transcription polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively. Treg content in patients with T1D was significantly decreased compared with the control volunteers. Treg content in rats was markedly decreased after injection with STZ to induce T1D rat model, while Treg infusion weakened the decrease. The change scope of weight and blood glucose in the model and Treg group was bigger than the control group, and the change in the infusion group was lighter than the model group. T1D decreased the expressions of IL-10, IL-4, TGF-β, and IL-2, while Treg infusion weakened the decrease. The expressions of IL-17 and IFN-γ in the T1D group was increased, while Treg infusion weakened the increase. Autologous Treg infusion can strengthen the immunologic and islet function to treat T1D which may be via regulating the expression of inflammatory factors.

Endotoxin and cytokine reducing properties of the oXiris membrane in patients with septic shock: A randomized crossover double-blind study.

BackgroundEndotoxin induces an inflammatory response, with secondary release of cytokines, which can progress to shock and multiple organ failure. We explored whether continuous renal replacement therapy (CRRT) using a modified membrane (oXiris) capable of adsorption could reduce endotoxin and cytokine levels in septic patients.MethodsSixteen patients requiring CRRT for septic shock-associated acute renal failure and who had endotoxin levels >0.03 EU/ml were prospectively randomized in a crossover double-blind design to receive CRRT with an oXiris filter or with a standard filter. Endotoxin and cytokine levels were measured at baseline and 1, 3, 8, 16 and 24 hours after the start of CRRT. Norepinephrine infusion rate and blood lactate levels were monitored.ResultsDuring the first filter treatment period, endotoxin levels decreased in 7 of 9 (77.8%) oXiris filter patients, but in only 1 of 6 (16.7%) standard filter patients (P = 0.02). Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and interferon (IFN)γ decreased more with the oXiris filter than with the standard filter. Lactate concentration decreased with oXiris (-1.3[-2.2 to -1.1] mmol/l, P = 0.02), but not with the standard filter (+0.15[-0.95 to 0.6]). The norepinephrine infusion rate was reduced during oXiris CRRT, but not during standard filter CRRT. In the second filter treatment period, there was no significant reduction in endotoxin or cytokine levels in either group.ConclusionsCRRT with the oXiris filter seemed to allow effective removal of endotoxin and TNF-α, IL-6, IL-8 and IFNγ in patients with septic shock-associated acute renal failure. This may be associated with beneficial hemodynamic effects.