Interferon-gamma Ratio Research Articles

Changes Resulting From Resistance Training in the Ratio of Interferon-gamma to Insulin-like Growth Factor 1 and Lipid Profile in Diabetic Rats

Background and Objectives Diabetes is associated with an increase in inflammatory markers and development of atrophy and cardiovascular diseases. Studies have shown that resistance training at appropriate intensity can reduce inflammation generally. This study aims to investigate the effect of a progressive resistance training (PRT) program on serum concentrations of interferon gamma (IFN-γ), and insulin-like growth factor 1 (IGF-1) and lipid profile in rats with type 1 diabetes. Subjects and Methods In this experimental study, 32 male Wistar rats aged 40 days and weighing 250±30 g were divided into four groups of healthy control, healthy trained, diabetic control, diabetic trained. Streptozotocin (55 μg/kg per body weight) was injected intraperitoneally to induce diabetes. A 6-week PRT protocol was performed, including climbing a ladder with weights at three sessions per week (one hour per day), where the load increased by 5% increase each week. Data were analyzed by ANOVA followed by Tukey’s post hoc test. The significance level was set at 0.05. Results There was no significant difference in IFN-γ level between the diabetic trained group and other groups (P>0.05). The IGF-1 level in diabetic trained group was significantly lower than in the healthy control and trained control groups (P=0.002). The ratio of IGF-1/IFN-γ in diabetic trained group was significantly lower than in the trained control (P=0.003) and healthy control (P=0.008) groups. In assessing the lipid profile, the cholesterol level was higher in the diabetic trained group compared to the healthy control group (P=0.028). Moreover, triglyceride level was significantly higher in the diabetic trained group compared to the diabetic control (P=0.033), trained control (P=0.003) and healthy control (P=0.002) groups. Conclusion Six weeks of PRT cannot lead to desired efficacy in diabetic rats compared to non-trained diabetic rats. However, the small changes such as increased IGF-1 and HDL levels and decreased serum glucose level, can help with the clinical improvement of patients with type 1 diabetes.

Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening

Natural killer (NK) cells play important roles in controlling virus-infected and malignant cells. The identification of new molecules that can activate NK cells may effectively improve the antiviral and antitumour activities of these cells. In this study, by using a commercially available metabolism-related compound library, we initially screened the capacity of compounds to activate NK cells by determining the ratio of interferon-gamma (IFN-γ)+ NK cells by flow cytometry after the incubation of peripheral blood mononuclear cells (PBMCs) with IL-12 or IL-15 for 18 h. Our data showed that eight compounds (nafamostat mesylate (NM), loganin, fluvastatin sodium, atorvastatin calcium, lovastatin, simvastatin, rosuvastatin calcium, and pitavastatin calcium) and three compounds (NM, elesclomol, and simvastatin) increased the proportions of NK cells and CD3+ T cells that expressed IFN-γ among PBMCs cultured with IL-12 and IL-15, respectively. When incubated with enriched NK cells (purity ≥ 80.0%), only NM enhanced NK cell IFN-γ production in the presence of IL-12 or IL-15. When incubated with purified NK cells (purity ≥ 99.0%), NM promoted NK cell IFN-γ secretion in the presence or absence of IL-18. However, NM showed no effect on NK cell cytotoxicity. Collectively, our study identifies NM as a selective stimulator of IFN-γ production by NK cells, providing a new strategy for the prevention and treatment of infection or cancer in select populations.

Serum interleukin-17A/interferon-gamma ratio as a predictor for the severity of atrial low voltage in atrial fibrillation: from FIB-MARK study

Abstract Background Atrial fibrosis is hallmark of structural remodeling in atrial fibrillation (AF), but the inflammatory mechanism remains unclear. The purpose of the present study was to identify the specific inflammatory biomarkers to atrial fibrosis evaluated by atrial low voltage (LV) in AF patients for clarification of the mechanism. Methods Forty inflammatory biomarkers were quantified in 16 consecutive AF patients measured left atrial low voltage during catheter ablation. Results Median %LV area was 17%. In Pearson's correlation analysis, interleukin (IL)-17A and interferon (IFN)-γ was the most significant positive and negative correlation with %LV (R=0.35 and 0.43, P<0.001). Furthermore, there was a significant correlation between IL-17A/IFN-γ ratio and %LV (R=0.65, P=0.007). The area under the receiver operator characteristics curve of IL-17A/IFN-γ ratio for significant LV (%LV >10% as a reference standard) was 0.88. IL-17A/IFN-γ ratio was significantly higher in patients with significant LV than those without (1.41 versus 0.97, P=0.01), Furthermore, the sensitivity, specificity, and accuracy for detecting significant LV were 60%, 100%, and 75.0% at the cutoff value of 1.3. The event free survival from recurrent atrial tachyarrhythmias was not significantly different between patients with and without IL-17A/IFN-γ ratio >1.3 (83.3% versus 80.0% at 1-year, P=0.81). Conclusions Among inflammatory biomarkers, IL-17A/IFN-γ ratio was a significant predictor for the severity of left atrial low voltage n AF patients. Further study is needed to reveal the association between IL-17A and IFN-γ for development of fibrosis in AF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI GrantNumber JP19K17594

Asthma, biologics, corticosteroids, and coronavirus disease 2019

Asthma, biologics, corticosteroids, and coronavirus disease 2019

Screening of Sceptridium ternatum for antitussive and antiasthmatic activity and associated mechanisms.

ObjectivesSceptridium ternatum is an expectorant in traditional Chinese medicine and is prescribed for the treatment of asthma. The study aim was to screen Sceptridium ternatum for ingredients with antitussive and antiasthmatic effects and to study their associated mechanisms.MethodsCough in mice was induced using ammonia. Cough latency and the number of coughs within 3 minutes were determined. Airway responsiveness was assessed using ovalbumin as a sensitizer and characteristic asthma indicators were measured.ResultsChloroform and ethyl acetate extracts significantly reduced the number of coughs within 3 minutes, tidal volume, and the percentage of eosinophilic granulocytes, lymphocytes and neutrophils. All extracts decreased airway responsiveness in asthmatic mice compared with the untreated group. Petroleum ether, chloroform and n-butanol extracts lowered the Penh values of asthmatic mice. Petroleum ether and ethyl acetate extracts greatly reduced interleukin-4 expression and the interleukin-4/interferon gamma ratio. Compared with the model group, all extracts reduced mRNA expression of the cysteinyl leukotriene receptor-1 (CysLT1).ConclusionsChloroform extract and ethyl acetate extract displayed obvious antitussive effects and reduced airway inflammation. Thus, these two extracts contain the effective ingredients of Sceptridium ternatum. The active mechanism was ascribed to inhibition of mRNA expression of the CysLT1 receptor in mice with bronchial asthma.

THE EFFECT OF ALPHA-MANGOSTIN IN BALANCING THE RATIO OF CYTOKINES PRO-AND ANTI-INFLAMMATION-GAMMA (IFN-γ/IL-10) AND SEVERITY OF THE DISEASE IN MICE INFECTED WITH MYCOBACTERIUM TUBERCULOSIS MULTIDRUG-RESISTANT

ABSTRACTObjective: The objective of this study was observed to measure the effect of alpha-mangostin in balancing the ratio of interferon-gamma (IFN-γ) andinterleukin-10 (IL-10), and the severity of the disease in mice which infected with Mycobacterium tuberculosis multidrug-resistant (TB-MDR).Method: Infected BALB/c mice were consisted of five groups: Treated with anti-TB drugs+α-mangostin, treated with anti-TB drugs, given α-mangostinduring treatment, and control group. Cytokine levels of culture supernatant of spleen cells were measured by enzyme-linked immunosorbent assay.The number of bacterial colonies was derived from a primary cell culture of bronchoalveolar lavage. Statistical analysis was performed with Anova,Kruskal-Wallis test and correlation Pearson, and Spearman-rank test.Result: Median IFN-γ production was higher in mice, which given with α-mangostin during treatment is 1838.2 pg/ml and control is 1585.5 pg/mlcompared treated with anti-TB drugs+α-mangostin (1312 pg/ml) and anti-TB drugs (1429.3 pg/ml) (p>0.05). The highest result production of medianIL-10 in the 3th group is (465.91 pg/ml) and the lowest in the control group is 195.29 pg/ml, p>0.05. Median IFN-γ/IL-10 ratio of the 3th group verylow (3.94), it means the 3th group is experienced with severity of TB. Alpha-mangostin was decreased in severity of disease based on the number ofTB-MDR bacterial colonies (p≤0.05).Conclusion: α-mangostin have an effect on the balancing IFN-γ/IL-10 ratio and reduce a severity of TB-MDR with using immunomodulator.Keywords: Tuberculosis multidrug-resistant, Alpha-mangostin, Interferon-γ/interleukin-10 ratio, Number of tuberculosis multidrug-resistantbacterial colonies.

Cytokine Pattern is Affected by Training Intensity in Women Futsal Players.

To find the relation between exercise and cytokines, we examined the effect of the training intensity on the levels of cytokines, including interferon-gamma (IFN-γ), interlukine-4 (IL-4) and interlukine-4/interferon-gamma ratio (IL-4/IFN-γ ratio) in female Futsal players. Twelve well-trained female college Futsal players aged 19~22 participated in this study. The athletes completed 30-min of running at 60~65% maximal heart rate [moderate-intensity exercise], and 30-min of running at 75~80% maximal heart rate [high-intensity exercise]. peripheral blood samples were collected 24 h before and 24 h and 48 h after each of the exercise bouts. finding showed that The 30-min bout of moderate-intensity exercise induced a significant increase in IFN-γ (p=0.01) and significant decreases in IL-4 (p=0.001) and IL-4/IFN-γ ratio (p=0.003). And also, 30-min of running at 75~80% maximal heart rate induced increase in IFN-γ (p=0.07) and decreased in IL-4 (p=0.01) and IL-4/IFN-γ ratio (p=0.06) that these changes not significantly. In summary, exercise intensity can effect on the magnitude of changes in cytokines. It seems that moderate intensity exercise enhances cytokine pattern in female college Futsal players.

Modulation of T cell response by Phellinus linteus

Phellinus linteus, a species of mushroom, has been shown to contribute to health benefits, such as anti-inflammatory activity and immunomodulatory efficacy. The aim of this study was to analyze the most effective constituents of P.linteus fermented broths, polysaccharides, and to evaluate their immunoregulatory effects on T cells. Four fermented broths (PL1-4) and the dialyzate medium (MD) were prepared from P.linteus mycelia, and the polysaccharide contents of each were analyzed. The P.linteus samples were tested for biological activity in the regulation of T cell activation. In T cells, the production of mitogen-induced interleukin (IL)-2 and cell cycle progression were dose-responsively inhibited by PL3 and MD, primarily through cell-cycle arrest in S phase. PL3 broth, which contained large quantities of polysaccharides, significantly decreased the ratio of interferon-gamma (IFN-γ) to interleukin 4 (IL-4) in T cells. Thus, P.linteus fermented broths produced additive effects on the regulation of the Th1/Th2 balance and show promise for the development of immunomodulatory therapeutics.

Differential effects of propofol and isoflurane on the activation of T‐helper cells in lung cancer patients

It is suggested that activation and differentiation of T-helper cells are required for peri-operative anti-tumor and anti-infection immunity. The present study aimed to evaluate whether propofol stimulates the activation and differentiation of these cells in patients undergoing pulmonary lobectomy for non-small-cell lung cancer. Thirty patients were randomly allocated to receive propofol or isoflurane throughout surgery. The CD4(+)CD28(+) percentage (p < 0.0001) and the ratio of interferon-gamma:interleukin-4 (p = 0.001) all increased with propofol but showed no change with isoflurane. In contrast, cortisol increased with isoflurane (p < 0.0001) but not with propofol over time (p = 0.06). We conclude that propofol promotes activation and differentiation of peripheral T-helper cells.

Probiotics during weaning reduce the incidence of eczema

A reduced microbial load early in life has been suggested to be linked to the increasing prevalence of allergic diseases in the industrialized world. Some studies have indicated that probiotics may be effective in the prevention of eczema. In vitro studies indicate that probiotics have immunomodulatory effects. In the present study, we evaluated the effects of feeding Lactobacillus F19 during weaning on the incidence of eczema and Th1/Th2 balance. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without Lactobacillus F19 (n = 90) from 4 to 13 months of age. We assessed the cumulative incidence of eczema at 13 months of age. The ratio of interferon-gamma (IFN-gamma) to interleukin 4 (IL4) mRNA expression levels in polyclonally stimulated peripheral blood T cells was used as a proxy for immune balance. Total and specific IgE serum levels were also assessed. The cumulative incidence of eczema at 13 months was 11% (4-17%, 95% CI) and 22% (13-31%, 95% CI) in the probiotic and placebo groups, respectively (p < 0.05). The number needed to treat was 9 (6.5-11.5, 95% CI). At 13 months of age, the IFN-gamma/IL4 mRNA ratio was higher in the probiotic compared with the placebo group (p < 0.05). In contrast, there were no differences between groups in serum concentrations of IgE. In summary, feeding Lactobacillus F19 during weaning could be an effective tool in the prevention of early manifestation of allergy, e.g., eczema. The higher Th1/Th2 ratio in the probiotic compared with the placebo group suggests enhancing effects of Lactobacillus F19 on the T cell-mediated immune response.

Cryptococcal Urease Promotes the Accumulation of Immature Dendritic Cells and a Non-Protective T2 Immune Response within the Lung

Urease, a major virulence factor for Cryptococcus neoformans, promotes lethal meningitis/encephalitis in mice. The effect of urease within the lung, the primary site of most invasive fungal infections, is unknown. An established model of murine infection that utilizes either urease-producing (wt and ure1::URE1) or urease-deficient (ure1) strains (H99) of C. neoformans was used to characterize fungal clearance and the resultant immune response evoked by these strains within the lung. Results indicate that mice infected with urease-producing strains of C. neoformans demonstrate a 100-fold increase in fungal burden beginning 2 weeks post-infection (as compared with mice infected with urease-deficient organisms). Infection with urease-producing C. neoformans was associated with a highly polarized T2 immune response as evidenced by increases in the following: 1) pulmonary eosinophils, 2) serum IgE levels, 3) T2 cytokines (interleukin-4, -13, and -4 to interferon-gamma ratio), and 4) alternatively activated macrophages. Furthermore, the percentage and total numbers of immature dendritic cells within the lung-associated lymph nodes was markedly increased in mice infected with urease-producing C. neoformans. Collectively, these data define cryptococcal urease as a pulmonary virulence factor that promotes immature dendritic cell accumulation and a potent, yet non-protective, T2 immune response. These findings provide new insights into mechanisms by which microbial factors contribute to the immunopathology associated with invasive fungal disease.

Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens

A key question in the field of autoimmunity concerns the fact that experimental disease is generally induced more easily with closely related, but not completely identical, tissue-restricted antigens. Here, the possibility that naturally occurring regulatory T cells (Tregs) for self-antigens are more potent than those for related antigens was investigated. The self-antigen specificity of naturally occurring Tregs was tested in experimental autoimmune encephalomyelitis (EAE) induced with mouse (self) or closely related (rat) myelin oligodendrocyte glycoproteins (MOGs). Surprisingly, Treg depletion increased EAE severity in mice immunized with mouse, but not rat, MOG. This increase was associated with increased T-cell activation and infiltration of the central nervous system, as well as increased interleukin (IL)-17 production and a higher ratio of interferon-gamma- to IL-10-producing cells. These data suggest that Tregs are specific for self-antigen and do not "cross-protect" against autoimmunity even when disease is induced with closely related foreign antigens.

Immunological characteristics of patients infected with common intestinal helminths: results of a study based on reverse-transcriptase PCR

To determine whether common helminth infections could modify the intestinal immunopathological status of the host, the expression in the human duodenal mucosa of cytokines, eosinophil- and mast-cell-specific molecules and monosaccharide transporters of the glucose-transporter (GLUT) family was explored. The 31 subjects were all patients at the gastro-intestinal disease unit of Nongkhai Hospital, Thailand. Four of the 10 patients who presented with eosinophilia (> or = 6.0% of their leucocytes were eosinophils), and five of the other 21 patients, had intestinal infections with helminths when they presented or within the previous 3 months. Studies based on semi-quantitative, reverse-transcriptase PCR revealed that the interleukin-5/interferon-gamma ratio was significantly higher in the noneosinophilic, helminth-infected patients than in the non-eosinophilic, uninfected patients, whereas the IgE receptor type I (Fc epsilon RI)/mast-cell tryptase ratio was significantly higher in the eosinophilic, helminth-infected patients than in the eosinophilic, uninfected patients. Expression of Charcot-Leyden-crystal protein, GLUT-1 and GLUT-5, however, showed no significant inter-group differences. Principal-components analysis of the data on eosinophils, interleukin-5, interferon-gamma, Fc epsilon RI and mast-cell tryptase revealed that one principal component could discriminate the patients who had helminth infection from the non-eosinophilic, uninfected patients, but not from the eosinophilic, uninfected patients. These results indicate that, whatever the intestinal pathology, patients infected with common intestinal helminths tend to develop a mucosal immunological response of the Th2 type.

The T-helper 1/T-helper 2 balance in peripheral blood of women with hyperemesis gravidarum

Objective: The purpose of this study was to evaluate the T-helper 1/T-helper 2 balance and its relation with pregnancy-related hormones in hyperemesis gravidarum. Study Design: The T-helper 1/T-helper 2 ratio and plasma progesterone and estrogen levels were examined in the peripheral blood of 22 women with hyperemesis gravidarum and normal pregnancies. The proportion of CD4-positive cells that expressed intracellular cytokines (interferon gamma and interleukin-4) were analyzed by blood flow cytometry. The ratio of interferon gamma–secreting cells to interleukin-4–secreting cells was taken as the T-helper 1/T-helper 2 ratio. Results: In hyperemesis gravidarum, the proportions of interleukin-4–secreting cells increased, and the T-helper 1/T-helper 2 ratio averaged 8.4 ± 0.9, which was significantly lower than in normal pregnancy (11.6 ± 1.1, P <.05). The changes in the T-helper 1/T-helper 2 ratio in hyperemesis gravidarum were accompanied by the elevation of progesterone and estrogen levels. Conclusion: A further shift of the T-helper 1/T-helper 2 balance to the T-helper 2 dominance in hyperemesis gravidarum may be related to the increase of progesterone and estrogen levels. (Am J Obstet Gynecol 2002;187:1631-5.)

Neonatal mycobacterial specific cytotoxic T-lymphocyte and cytokine profiles in response to distinct BCG vaccination strategies.

This study evaluated whether different bacillus Calmette-Guérin (BCG) strains, routes of administration, vaccination age and percutaneous tools influenced immune responses to BCG vaccination in infants. Proliferative responses, cytokine production and cell-mediated cytotoxicity obtained in post-vaccinated children were compared to baseline cord bloods and unvaccinated 10-week-old infants. BCG vaccination generally induced strong lymphoproliferative and T helper type 1 (Th1)-type cytokine responses. There was a trend for greater responsiveness following the intradermal route of vaccination, with Japanese-172 strain and with delaying vaccination until 10 weeks. Cord mononuclear cells differentially stimulated the Th2-type cytokines interleukin-5 (IL-5) and IL-10 selectively in response to BCG, as compared to H37Rv or purified protein derivative stimulation. We document for the first time the generation of mycobacterium-specific cytotoxic T lymphocytes in neonates, following BCG vaccination. Cytotoxic activity correlated with the ratio of interferon-gamma to IL-5, aside from a single instance where use of the Biovac tool resulted in a striking dissociation selectively against H37Rv targets. These data have implications for correlates of protective immunity in design of vaccine studies.

Intragraft overexpression of interleukin-4 is neither sufficient nor essential for tolerance induction to cardiac allografts in a high-responder strain combination.

Recently we have demonstrated that the nondepleting anti-CD4 monoclonal antibody (mAb) RIB5/2 induces long-term acceptance of kidney and heart allografts in all rat strain combinations tested. Cytokine gene expression studies by reverse transcriptase-polymerase chain reaction revealed a reversed intragraft interleukin (IL)-4/interferon-gamma ratio. Whether IL-4 mediated immune deviation contributes to transplantation tolerance is not clear so far. To learn more about the functional relevance of the relative IL-4 up-regulation, IL-4 was overexpressed in rat heart allografts by using ex vivo adenoviral gene transfer. The efficiency of gene transfer was analyzed by reporter gene assays as well by reverse transcriptase-polymerase chain reaction analysis of IL-4 mRNA expression. The intragraft overexpression of IL-4 did not prolong the allograft survival compared with controls. Moreover, neutralization of IL-4 by OX81 mAb did not prevent tolerance induction by RIB5/2 treatment. Anti-CD4 mAb-induced tolerance is associated with an intragraft type1/type2 shift, however, the up-regulation of IL-4 alone is neither sufficient nor essential to induce tolerance to cardiac allografts in a high-responder strain combination.

Chemically modified antigen preferentially elicits induction of Th1-like cytokine synthesis patterns in vivo.

Differential activation of CD4+ T cell subsets in vivo leads to the development of qualitatively different effector responses. We identify an approach that allows selective activation of strongly Th1-dominated immune responses to protein antigens. Whereas in vivo administration of ovalbumin (OVA) induces cytokine synthesis that is neither Th1 nor Th2 dominated, administration of glutaraldehyde polymerized, high relative molecular weight OVA (OA-POL) leads to 20-fold increase in the ratio of interferon gamma (IFN-gamma)/IL-4 and IFN-gamma/IL-10 synthesis observed after short-term, antigen-mediated restimulation directly ex vivo. In contrast, concurrent in vivo administration of anti-IFN-gamma mAb and OVA or OA-POL results in marked increases in IL-4 and IL-10, and decreased IFN-gamma production, reflecting a polarization of the response towards a Th2-like pattern of cytokine synthesis. These observations may be useful in clinical settings including hypersensitivity, autoimmune diseases, and vaccine development where the ability to actively select specific patterns of cytokine gene expression would be advantageous.