IFN-α Levels Research Articles

Improvement of Cyclophosphamide-Induced Immunosuppression by Miaoyao Fanggan Sachet Extract

Chemotherapy drugs, such as cyclophosphamide, often produce side effects of immunosuppression in the treatment of tumors. This study investigated whether the Miaoyao Fanggan sachet extracts—diammonium glycyrrhizinate and magnesium isoglycyrrhizinate—can regulate respiratory immunity in mice. A cyclophosphamide-induced immunosuppressive mice model was treated with diammonium glycyrrhizinate and magnesium isoglycyrrhizinate. Interferon (IFN)-α, interferon-β, interleukin (IL)-6, and interleukin-18 levels in the bronchoalveolar lavage fluid and lung tissue were detected using enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction, respectively. The p-(phospho) transforming growth factor beta-activated kinase 1 (TAK1)/TAK1 and p-IkappaB (IκB)/IκB in the lung tissue and bronchial mucosa were detected by Western blot. Compared with the control group, the IFN-α and IL-6 levels decreased, while IFN-βand IL-18 levels increased in the mice model. However, these changes were reversed with the treatment with diammonium glycyrrhizinate and magnesium isoglycyrrhizinate; p-TAK1/TAK1 and p-IκB/IκB in the model group decreased significantly and increased with the increasing treatment dose of diammonium glycyrrhizinate and magnesium isoglycyrrhizinate. Diammonium glycyrrhizinate and magnesium isoglycyrrhizinate had a certain effect on cyclophosphamide-induced immunosuppression in mice, likely mediated through the phosphorylation of TAK1 and IκB, activating nuclear factor kappa-B and subsequently stimulating the Janus kinase/signal transducer and activator of transcription/mitogen-activated protein kinase pathway.

Chemokines and Cytokines Profiles in Patients with Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis: A Preliminary Study.

The damage to small vessels in AAV and inflammatory reactions are accompanied by the release of various chemokines and cytokines. Using a flow cytometry technique, we assessed the levels of specific cytokines, namely IL-1β IL-6, IL-8, IL-10, IL12p70, and TNF, and chemokines, IFN-α, IP-10, and MIG in the serum from 9 healthy volunteers and 20 AAV patients, where 11 of the patients were not treated and evaluated at the time of diagnosis and 9 were already diagnosed and taking CY + GCS. The obtained results were then compared considering the activity of the disease, the type and titre of the ANCA antibodies, the inflammatory status, and the kidneys' condition. Amongst others, the IL-6, IL-8, IL-10, TNF, and MIG levels were much higher in the serum of AAV patients than in healthy controls, whereas the level of IL-1β was higher in healthy volunteers. Additionally, the levels of IL-6, IL-10, IP-10, and MIG negatively correlated with the eGFR level, while the level of IFN-α positively correlated with the titre of PR3-ANCA. As most of the molecules are implicated in trafficking primed neutrophils towards small vessels, looking for links between the levels of these cytokines/chemokines and the clinical symptoms of AAV may facilitate the diagnosis and predict the progression of the disease.

Proinflammatory Cytokine Profiles in Both Mild Symptomatic and Asymptomatic SARS-CoV-2-Infected Egyptian Individuals and a Proposed Relationship to Post-COVID-19 Sequela.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with proinflammatory cytokine release as mediators of host antiviral response to the infection. Cytokine persistent elevation leads to post-Coronavirus disease-2019 (COVID-19) post-COVID-19 sequela (PCS) reported in about 60% of patients affecting individual's normal life after recovery. This study evaluates relationship of cytokines and chemokines pattern during and postinfection to PCS events. Serum samples collected from 82 individuals with symptomatic, asymptomatic, or no SARS-CoV-2 infection were classified as recently or formerly infected groups according to levels of anti-2019nCoV Immunoglobulin G/Immunoglobulin M. Levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, interferon alpha (IFN-α), tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 were assessed via ELISA for each individual. All asymptomatic groups showed nonsignificant differences in cytokines' levels than control group. Significant elevation of IFN-α, TNF-α, and GM-CSF levels were observed in recent symptomatic, while IFN-α and TNF-α levels were significant in former symptomatic groups. We observed an association between fever with IL-1α and IFN-α levels, fatigue with TNF-α and GM-CSF, dyspnea with IFN-α, TNF-α, and GM-CSF, and chest-wheezing with GM-CSF. Individuals were surveyed 12 months postsampling for PCS events. Among 35 responders to survey, 8 (22.8%) reported PCS events, 6 of which were females. Upon studying PCS events, IL-8, IFN-α, TNF-α, and GM-CSF levels showed significant elevation in active infection, that was not seen in a resolved state of infection. Cytokines patterns suggest that either a persistent elevation in levels or damage caused during infection contributes to PCS. Although with the limited sample size, our study emphasizes the importance to conduct medical approaches targeting the associated cytokines to improve the PCS symptoms.

Expression Pattern of Cholesterol 25-Hydroxylase and Serum Level of 25-Hydroxycholesterol and Relevant Inflammatory Cytokines in Patients with Varying Disease Severity of COVID-19.

Cholesterol 25-hydroxylase (CH25H) and its product 25-hydroxycholesterol (25HC) showed antiviral effects against various viruses in vitro. CH25H expression is regulated in mice by pro-inflammatory cytokine interferons (IFNs) in mice but data on its possible correlation with IFNs in humans are still unclear. We examined gene expression of CH25H, IFN-α, and IFN-β and serum levels of 25HC in Iranian patients with mild and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Fifty intensive care unit (ICU) patients and outpatients with SARS-CoV-2 and 25 healthy controls were studied. Gene expression of CH25H and relevant inflammatory cytokines was quantified in peripheral blood mononuclear cells by real-time polymerase chain reaction. The expression of CH25H and serum levels of 25HC were significantly higher in ICU patients with SARS-CoV-2. Notably, IFN-α levels increased in healthy controls. However, compared to healthy controls, IFN-β was considerably higher in outpatients. Finally, statistical analysis shows that no correlation was found between CH25H and IFN-α expression; nevertheless, a lower correlation was found with IFN-β. The data revealed that CH25H and 25HC levels increase after SARS-CoV-2 infection. In other words, decreased levels of those factors in severe patients compared with mild patients may indicate the importance of their function in controlling the progression of the disease.

Baicalin mitigates nephropathogenic infectious bronchitis virus infection-induced spleen injury via modulation of mitophagy and macrophage polarization in Hy-Line chick

Nephropathogenic infectious bronchitis virus (NIBV) infections continue to pose a significant hazard in the poultry industry. Baicalin is a natural flavonoid that has been reported to have antiviral activity, but its function in NIBV infection largely remains unclear. In this study, the antiviral mechanism of baicalin in the spleen of NIBV-infected chicks was mainly elucidated in mitophagy and macrophage polarization. 28-day-old Hy-Line brown chicks were randomly divided into four groups: the group of chicks was treated intranasally (in) with normal saline (0.2 mL) and subsequently divided into two groups: the Con group (basic diet), the Con+BA group (basic diet+10 mg/kg Baicalin); another group of chicks was intranasally infected with SX9 (10−5/0.2 mL) and subsequently divided into two groups: the Dis group (basic diet), the Dis+BA group (basic diet+10 mg/kg Baicalin). Spleen tissues were collected at 3, 7, and 11 days post infection (dpi). NIBV copy number was strikingly decreased in the spleens under BA treatment with infectious time. Histopathological examination showed enlarged and hemorrhagic white pulp and no clearly defined boundary between white pulp and red pulp in the Dis group, which could be improved by BA treatment. Meanwhile, the loss of cristae structure and vacuolization in mitochondria caused by NIBV infection was repaired in the Dis+BA group by ultrastructure observation. In addition, BA treatment inhibited the induction of mitophagy by NIBV infection. BA treatment also promoted innate immunity by enhancing type I IFN levels. Moreover, BA treatment up-regulated M1-related cytokines (iNOS, TNF-α, IL-1β, IL-6) and inhibited M2-related cytokines (ARG2, IL-4, IL-10, Pparg) at the mRNA and protein levels. However, the results from the splenic tissues at 11 dpi are opposite results from 3 and 7 dpi. Immunofluorescence analysis for M1 macrophage marker iNOS and M2 macrophage marker CD163 further validated this result. Collectively, BA inhibited mitophagy and triggered IFN activation, and M1 polarization, which contributed to the inhibition of NIBV infection.

FAdV-4 Promotes Expression of Multiple Cytokines and Inhibits the Proliferation of aHEV in LMH Cells.

Single or mixed infections of multiple pathogens such as avian hepatitis E virus (aHEV) and avian leukosis virus subgroup J (ALV-J) have been detected in numerous laying hens with severe liver injury in China. Thus, aHEV and immunosuppressive viruses are speculated to cause co-infections. In this study, co-infection with aHEV and fowl adenovirus (FAdV) was confirmed by nested RT-PCR and recombinase-aided amplification combined with gene sequencing in two flocks with severe liver injury. Subsequently, the two reference strains, aHEV and FAdV-4, were inoculated into LMH cells to identify their co-infection potential. Confocal microscopy revealed aHEV and FAdV-4 co-infected LMH cells. In addition, the replication dynamics of aHEV and FAdV-4 along with the expression levels of immuno-cytokines were measured. The results indicated colocalization of aHEV and FAdV-4 and inhibition of viral replication in LMH cells. The transcription levels of MDA5, Mx, OASL, and IFN-α were significantly upregulated in LMH cells, whereas those of immune-related factors induced by FAdV-4 were downregulated upon FAdV-4 and aHEV co-infection. These results confirmed the co-infection of aHEV and FAdV-4 in vitro and prompted the antagonistic pathogenic effects of FAdV-4 and aHEV, thereby providing novel insights into the counterbalancing effects of these viruses.

Clinical, Virological, and Immunological Features in Cosmopolitan Genotype DENV-2-Infected Patients during a Large Dengue Outbreak in Sri Lanka in 2017.

In 2017, Sri Lanka experienced its largest dengue epidemic and reported severe and unusual presentations of dengue with high morbidity. This outbreak was associated with the reemergence of dengue virus-2 (DENV-2), with the responsible strain identified as a variant of the previously circulating DENV-2 cosmopolitan genotype. In this study, we characterized the DENV-2 cosmopolitan genotype from patients during this epidemic. Also, we identified host factors that contributed to the severity of dengue infection in patients infected with this particular virus. Ninety-one acute serum samples from patients at the National Hospital in Kandy were randomly selected. Of these, 40.2% and 48.9% were positive for dengue IgM and IgG, respectively. NS1 antigen levels were significantly higher in primary infections. The severe dengue (SD) and dengue with warning signs (DWWS) groups exhibited significantly higher viral genome and infectivity titers than the dengue without warning signs (DWoWS) group. The highest viremia level was observed in SD patients. As for host cytokine response, interferon α (IFN-α) levels were significantly higher in the DWoWS group than in the DWWS and SD groups, whereas interleukin (IL)-12p40 and tumor necrosis factor α (TNF-α) levels in SD patients were significantly higher than in the other two groups. The TNF-α, IL-4, and monocyte chemoattractant protein-1 concentrations were positively correlated with NS1 antigen levels. From whole-genome analysis, NS4 had the highest frequency of amino acid variants, followed by the E gene. Our study suggests that viremia levels and immune responses contributed to SD outcomes, and these findings may help in identifying an effective therapeutic strategy against SD infection.

Interferon regulatory factor 7 modulates virus clearance and immune responses to alphavirus encephalomyelitis.

Viral encephalomyelitis outcome is dependent on host responses to neuronal infection. Interferon (IFN) is an important component of the innate response, and IFN regulatory factor (IRF) 7 is an inducible transcription factor for the synthesis of IFN-α. IRF7-deficient mice develop fatal paralysis after CNS infection with Sindbis virus, while wild-type mice recover. Irf7 -/- mice produce low levels of IFN-α but high levels of IFN-β with induction of IFN-stimulated genes, so the reason for this difference is not understood. The current study shows that Irf7 -/- mice developed inflammation earlier but failed to clear virus from motor neuron-rich regions of the brainstem and spinal cord. Levels of IFN-γ and virus-specific antibody were comparable, indicating that IRF7 deficiency does not impair expression of these known viral clearance factors. Therefore, IRF7 is either necessary for the neuronal response to currently identified mediators of clearance or enables the production of additional antiviral factor(s) needed for clearance.

Association of Inflammatory Cytokine Levels with Extra Glandular Manifestations, Fatigue, and Disease Activity in Primary Sjögren's Syndrome in Saudi Patients: A Cross-Sectional Study.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that can cause fatigue and extraglandular manifestations (EGMs). pSS is associated with cytokine network dysregulation, which may be related to the immune-mediated destruction of exocrine glands. We determined cytokine levels and their relationship to EGMs, the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI), and fatigue in Saudi patients with pSS. This study was a cross-sectional, single-center study. We included forty-one patients and 71 controls. Serum samples were collected from random healthy people and pSS patients who were followed in the rheumatology and pulmonary clinics of King Saud University Medical City in Riyadh, Saudi Arabia. Levels of the frequently studied cytokines were measured using Luminex xMAP technology. Each ESSDAI score and EGM were recorded, and the Arabic version of the fatigue severity scale (FSS) was applied to assess fatigue. The main outcome measures were cytokine levels in pSS Saudi patients using/not using immune-suppressive medications (ISMs). Thirty-six (87.8%) patients had one or more EGMs, and the mean ESSDAI score was 9.95 ± 7.73. There was a significant decrease in TNFα and IL-21 levels in the pSS group compared to those in the control group (p = 0.034 and p < 0.001, respectively), whereas IL-12 levels were significantly elevated in the pSS group (p = 0.002). Cytokine levels in patients who used ISMs were the same as those in patients who did not use medications. Decreased IL-1β (p = 0.014), IL-2 (p = 0.035), IL-6 (p = 0.014), and IL-35 (p = 0.010) levels were observed in patients who had EGMs. Patients who had low disease activity exhibited low IL-10 (p = 0.018) and high IFN-α (p = 0.049), IFN-β (p = 0.049), IL-1β (p = 0.006), and IL-35 (p = 0.032) levels compared to patients with high disease activity. A negative association between a positive fatigue score and IL-1β (p = 0.010), IL-2 (p = 0.037), IFN-α (p = 0.025), TNFα (p = 0.030), IL-17 (p = 0.029), IL-12 (p = 0.046), and IL-21 (p = 0.005) levels was found. Cytokine profiles correlate with EGMs, ESSDAI, and fatigue. Patients with controlled disease activity have a normal cytokine profile that is similar to that of controls.

Сytokines as non-hormonal regulators in the pathogenesis of endocrinopathies

Cytokines regulate the activity of hypothalamus – pituitary – adrenal hormonal axis, also affecting thyroid gland and ovaries. However, their exact role in pathogenesis of endocrine diseases is still under study. Altered cytokine secretion in autoimmune thyroid diseases and polycystic ovary syndrome is well known. Meanwhile, the main immunological predictors of severe prognosis in endocrinopathies and biomarkers for administration of targeted immunotherapy have not yet been determined. Therefore, our objective was to study the relationships between the cytokines and hormones in pathogenesis of autoimmune and non-autoimmune endocrinopathies, i.e., autoimmune thyroiditis (AIT), Graves’ disease (GD), nodular and multinodular goiter, polycystic ovary syndrome (PCOS).&#x0D; 101 patients with GD and 105 patients with AIT, 110 patients with PCOS were examined; 51 patients with nodular and multinodular euthyroid goiter and 50 healthy individuals; their average age was 34.5±2.9 years old. The study was approved by the Interdisciplinary Ethics Committee of the Pacific State Medical University. Clinical examination included ultrasonography. ELISA technique was applied for determination of thyroid and sex hormones, TSH, autoantibodies to TPO, TSH receptor, cytokines in blood serum, in follicular fluid samples, cell culture media (primary cultures of cumulus cells). Genetic studies were carried out with PCR. Morphological verification was performed by inverted microscopy CKX41 (Olympus) with a phase contrast system, camera AxioCam5 (Carl Zeiss) with software Zen 2, Blue Edition.&#x0D; IL-6 and TNFα in the blood serum of patients with PCOS were most significantly increased, Sharply decreased IFNγ/IL-10 ratio in blood serum and cumulus cell culture was found in PCOS when compared with controls. Significant changes in the content of thyroid hormones in GD and TSH in AIT have been proven to affect the hyperproduction of pro- and anti-inflammatory cytokines. Before treatrment, the direct or reverse corelations were found between the levels of cytokines and thyroid hormones in GD, and TSH in AIT. Subsequently, upon correction of hormonal disorders, these associations became weaker, or faded away. In patients with nodular and multinodular euthyroid goiter, only the IFNγ level was significantly increased, being twice as high as in the control group.&#x0D; A significant imbalance in the ratio of Th1/Th2 marker cytokines and their hyperproduction in autoimmune thyroid diseases made it possible to characterize the cellular response system in autoimmune thyroid disorders as highly active and directly associated with thyroid dysfunction, performing its effector function under the impaired immunoregulation. The revealed changes in pro-inflammatory cytokines in polycystic ovary syndrome represent new immunological markers of fertility, which may be a promising target for pathogenetic immunotherapy.

Leukocyte cytokine expression is associated with severity of autism in children

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with unknown etiology, high clinical heterogeneity and marked aberrations of the immune system. Evidence for an association between immune dysfunction and behavioral traits highlights the need for a study of the immune cell functional activity in order to search for pathogenesis mechanisms and potential targets for therapy at ASD. The purpose: to determine the expression levels of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-18, IFNγ and TNFα in peripheral blood leukocytes of children with mild and severe ASD. The study included 81 children with ASD (77.8% boys) and 45 children with typical neurodevelopment (TDC, 71.1% boys). According to the Childhood Autism Rating Scale, 51 children (63.0%) had mild autistic symptoms (CARS score 32.0±1,5) and 30 children had severe ASD symptoms (CARS score 39.0±3,4). Cytokines expression in leukocytes was determined by quantitative PCR with SYBRGreen. The data were transformed using Box–Cox transformation. The differences between groups were assessed by one-way ANOVA and Dunn’s test for multiple comparisons. In leukocytes of children with ASD, regardless of the severity, the expression of IL-1β, IL-18 and IL-2, was significantly reduced compared to TDC. Moreover, in children with mild ASD, low expression of TNFα, compared with TDC was found. In children with severe ASD, the expression of the main cytokine of Th1 – IFNγ, was significantly increased, without an increased expression of an important cytokine of Treg – IL-10. Activation of the Th1 adaptive immune response without compensation by cytokines of Treg, the number of which is reduced in ASD, can lead to increased inflammation, even in the central nervous system, and correlates with the severity of ASD clinical symptoms. Despite extensive immunological evidence suggesting immune system dysregulation, further research is required to clarify the relationship between immune system cell function and ASD pathology.

Nailfold capillaroscopy in Egyptian systemic lupus erythematosus (SLE) patients: correlation with demographic features and serum levels of IL 17A and IFNs I

BackgroundIn SLE patients, cytokines are linked to endothelial cell damage. Nailfold capillaroscopy (NFC) is a simple method for evaluating micro-vascular abnormalities in different connective tissue diseases (CTDs). The study aimed to detect the levels of interleukin 17A (IL 17A), type I interferons (IFNs I) in the serum, and NFC changes in Egyptian SLE patients compared to a control group and to correlate NFC findings with patients’ demographic features and serum levels of IL 17A and IFNs I.ResultsSerum levels of IL 17A, IFN α, and IFN β were significantly higher in SLE patients than in control group (P < 0.0001). About thirty nine patients (73.6%) of the 53 SLE patients showed abnormal NFC changes. Egyptian SLE patients had a high prevalence of the NFC non-specific pattern, with 32 (60.4%) patients showing non-specific changes and 7 (13.2%) patients showing scleroderma pattern, including 3 (5.6%) patients with active scleroderma pattern and 4 (7.55%) patients with late scleroderma pattern. Furthermore, Raynaud’s phenomenon (RP) was observed in 8 (15.1%) SLE patients, with 3 (5.6%) having normal NFC pattern and 5 (9.4%) having scleroderma pattern. All controls (n = 20) showed normal hairpin shape capillaries. Except for SLEDAI (P = 0.03) and the presence of RP (P < 0.0001), there were no significant differences in demographic and laboratory parameters between the three NFC patterns (normal, non-specific, and scleroderma); additionally, NFC score correlated significantly with SLEDAI (P = 0.021).ConclusionAs a result of the high disease activity, Egyptian SLE patients had elevated serum levels of IL 17A and IFNs I. The most common NFC pattern in Egyptian SLE patients was a non-specific pattern. NFC abnormalities in Egyptian SLE patients were correlated with disease activity but not with patients’ ages, disease duration, or serum levels of IL 17A and IFNs I. SLE patients with scleroderma NFC pattern and RP should be closely followed for the possibility of appearance of anti-U1 RNP antibodies and MCTDS.

Black carp RIOK3 suppresses MDA5-mediated IFN signaling in the antiviral innate immunity

In mammals, right open reading frame kinase 3 (RIOK3) is related with cancer development and immune regulation. To explore the role of teleost RIOK3 in the antiviral innate immunity, the homolog of RIOK3 (bcRIOK3) from black carp (Mylopharyngodon piceus) has been cloned and characterized in this study. Sequence analysis revealed that bcRIOK3 is conserved in vertebrates. The transcription of bcRIOK3 varied in host cells in response to the stimulation of spring viremia of carp virus (SVCV), poly (I:C), and LPS. Immunoblotting (IB) and immunofluorescence (IF) assays identified bcRIOK3 as a cytoplasmic protein with a molecular weight of ∼60 kDa. It was interesting that bcRIOK3 knockdown led to the decreased basal mRNA levels of IFNa, IFNb and Viperin; however, triggered obviously higher mRNA levels of the above genes after viral infection and enhanced host resistance to SVCV. Like its mammalian counterpart, bcRIOK3 overexpression in EPC cells showed a significant inhibitory effect on black carp MDA5 (bcMDA5)-mediated transcription of interferon promoters and antiviral activity. Co-immunoprecipitation and immunofluorescent assays identified the association between bcRIOK3 and bcMDA5. Further analysis revealed that bcRIOK3 enhanced the K48-linked ubiquitination and proteasome-dependent degradation of bcMDA5, and it weakened the oligomerization of bcMDA5 under poly (I:C) stimulation. In summary, our data conclude that RIOK3 dampens MDA5-mediated IFN signaling by promoting its degradation in black carp, which provide new insights into the regulation of IFN signaling in teleost.

Pro-inflammatory markers associated with COVID-19-related persistent olfactory dysfunction.

While localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID-19) olfactory dysfunction (OD), persistent COVID-19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling. COVID-19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID-19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti-viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann-Whitney tests with multi-comparison adjustment. Viral RNA was assessed through RT-PCR using the COVID-19 N2 primer. Thirty-five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non-COVID no OD). Significant differences in IFN-λ1 (p = 0.007) and IFN-γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN-α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN-γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non-COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts. IFN pathway cytokines were found elevated in the olfactory microenvironment of COVID-19 persistent OD compared to those with no OD and no prior history of COVID-19 infection.

Serum interferon-alpha predicts in-hospital mortality in patients hospitalised with acute severe lupus

ObjectivesDysregulation of interferon-alpha (IFN-α) is considered central to the immunological abnormalities observed in SLE. Short-term mortality during high disease activity in lupus is up to 30%. Adenovirus vector-introduced IFN-α into...

Dynamics of Cytokine, SARS-CoV-2-Specific IgG, and Neutralizing Antibody Levels in COVID-19 Patients Treated with Convalescent Plasma.

Coronavirus disease 2019 (COVID-19) is a contagious illness worldwide. While guidelines for the treatment of COVID-19 have been established, the understanding of the relationship among neutralizing antibodies, cytokines, and the combined use of antiviral medications, steroid drugs, and convalescent plasma therapy remains limited. Here, we investigated the connection between the immunological response and the efficacy of convalescent plasma therapy in COVID-19 patients with moderate-to-severe pneumonia. The study included a retrospective analysis of 49 patients aged 35 to 57. We conducted clinical assessments to determine antibody levels, biochemical markers, and cytokine levels. Among the patients, 48 (98%) were discharged, while one died. We observed significantly higher levels of anti-nucleocapsid, anti-spike, and neutralizing antibodies on days 3, 7, and 14 after the transfusion compared to before treatment. Serum CRP and D-dimer levels varied significantly across these four time points. Moreover, convalescent plasma therapy demonstrated an immunoregulatory effect on cytokine parameters, with significant differences in IFN-β, IL-6, IL-10, and IFN-α levels observed at different sampling times. Evaluating the cytokine signature, along with standard clinical and laboratory parameters, may help to identify the onset of a cytokine storm in COVID-19 patients and determine the appropriate indication for anti-cytokine treatment.

A Double-Blind, Randomized Controlled Trial of Hydroxychloroquine for Cognitive Dysfunction and Inflammatory Biomarkers in Systemic Lupus Erythematosus Patients in Indonesia

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by persistent, chronic inflammation that damages organ tissue. One of the symptoms that is often found in SLE is cognitive dysfunction. Hydroxychloroquine is recommended for the treatment of all levels of SLE. This study was conducted to prove the influence of hydroxychloroquine on improving cognitive function and inflammatory biomarkers compared to standard therapy.METHODS: The study adopted randomized controlled trial (RCT) in SLE patients with cognitive dysfunction who met the inclusion criteria. The treatment group consisted of 26 subjects who received hydroxychloroquine 200 mg/day for 8 weeks and standard therapy, while the control group consisted of 29 subjects who were given standard therapy only. Examination of Montreal Cognitive Assessment (MoCA)-INA, interleukin (IL)-6, IL-4, interferon (IFN)-α, and C-reactive protein (CRP) scores was carried out at the beginning and the end of the study. The unpaired variables were examined with independent T-test or the Mann-Whitney test, while the paired variables were examined with paired T-test or Wilcoxon signed rank test. The Spearman correlation test was used to measure correlation between variables.RESULTS: A total of 55 subjects participated and completed the study. The result showed a significant relationship between hydroxychloroquine and decreasing levels of IL-6 and IL-4 (p&lt;0.05). Meanwhile, there was no significant effect on the increase in cognitive function and decrease in IFN-α and CRP (p&gt;0.05) in both groups.CONCLUSION: Hydroxychloroquine decreases the levels of IL-6 and IL-4, but has no effect on cognitive function, levels of IFN-α and CRP.KEYWORDS: hydroxychloroquine, systemic lupus erythematosus, cognitive dysfunction, inflammation

Glutamine improves growth and intestinal health in juvenile hybrid groupers fed high-dose glycinin

Glutamine addition can improve immunity and intestinal development in fish. This study examined the protective roles of glutamine on growth suppression and enteritis induced by glycinin in juvenile hybrid groupers (female Epinephelus fuscoguttatus × male Epinephelus lanceolatus). The experiment set four isonitrogenous and isolipidic trial diets: a diet containing 10% glycinin (11S), 10% of 11S diet supplemented with 1% or 2% alanine-glutamine (1% or 2% Ala-Gln), and a diet containing neither 11S nor Ala-Gln (FM). A feeding trial was conducted in hybrid grouper for 8 weeks. Weight gain and specific growth rates in Groups 1% and 2% Ala-Gln were significantly higher than those of the 11S group but were similar to those of the FM group. The intestinal muscular layer thickness, plica height and width of the 2% Ala-Gln group were significantly higher than those of Group 11S. The enterocyte proliferation efficiency of the 11S group was significantly lower compared to other groups. Compared with the 11S group, Groups 1% and 2% Ala-Gln fish had increased intestinal lysozyme activities, complement 3 and immunoglobulin M as well as cathelicidin contents. The mRNA levels of tnf-α, il-1β, ifn-α, and hsp70 genes were more downregulated in Groups 1% and 2% Ala-Gln than in Group 11S. Compared with FM group, fish from the 11S group had significantly lower mRNA levels of myd88, ikkβ, and nf-κb p65 genes. These three values in the 2% Ala-Gln group were significantly lower than those in Group 11S but not significantly different from those of Group FM. The relative abundance of Vibrio in Group 11S was higher than that in Groups FM and 2% Ala-Gln. Intestinal glutamine, glutaminase, glutamic acid, α-ketoglutarate, malate dehydrogenase and ATP contents were higher in Groups 1% and 2% Ala-Gln than in Group 11S. These results suggest that glutamine is a useful feed additive to enhance growth and intestinal immunity, alleviate inflammation, and modulate gut microbiota in hybrid grouper fed high-dose glycinin.

First Identification and Pathogenicity Evaluation of an EV-G17 Strain Carrying a Torovirus Papain-like Cysteine Protease (PLCP) Gene in China.

Enterovirus G (EV-G) is prevalent in pig populations worldwide, and a total of 20 genotypes (G1 to G20) have been confirmed. Recently, recombinant EV-Gs carrying the papain-like cysteine protease (PLCP) gene of porcine torovirus have been isolated or detected, while their pathogenicity is poorly understood. In this study, an EV-G17-PLCP strain, 'EV-G/YN23/2022', was isolated from the feces of pigs with diarrhea, and the virus replicated robustly in numerous cell lines. The isolate showed the highest complete genome nucleotide (87.5%) and polyprotein amino acid (96.6%) identity in relation to the G17 strain 'IShi-Ya4' (LC549655), and a possible recombination event was detected at the 708 and 3383 positions in the EV-G/YN23/2022 genome. EV-G/YN23/2022 was nonlethal to piglets, but mild diarrhea, transient fever, typical skin lesions, and weight gain deceleration were observed. The virus replicated efficiently in multiple organs, and the pathological lesions were mainly located in the small intestine. All the challenged piglets showed seroconversion for EV-G/YN23/2022 at 6 to 9 days post-inoculation (dpi), and the neutralization antibody peaked at 15 dpi. The mRNA expression levels of IL-6, IL-18, IFN-α, IFN-β, and ISG-15 in the peripheral blood mononuclear cells (PBMCs) were significantly up-regulated during viral infection. This is the first documentation of the isolation and pathogenicity evaluation of the EV-G17-PLCP strain in China. The results may advance our understanding of the evolution characteristics and pathogenesis of EV-G-PLCP.

Host immunity and HBV S gene mutation in HBsAg-negative HBV-infected patients.

Clinically, some patients whose HBsAg becomes negative owing to antiviral therapy or spontaneously still show a low level of HBV DNA persistence in serum. T-lymphocyte subsets, cytokine levels and HBV S gene sequences were analyzed in this study. A total of 52 HBsAg-negative and HBV DNA-positive patients(HBsAg-/HBV DNA+ patients), 52 persistently HBsAg-positive patients(HBsAg+/HBV DNA+ patients) and 16 healthy people were evaluated. T-lymphocyte subsets of these patients were detected by flow cytometry, serum cytokines and chemokines were detected by the Luminex technique, and the HBV S region was evaluated by Sanger sequencing. T%, T-lymphocyte, CD8+ and CD4+T lymphocyte were lower in the HBsAg-negative group than in the HC group. Compared with the HBsAg-positive group, the HBsAg-negative group had lower levels in T lymphocyte %, CD8+T lymphocyte %, CD8+T lymphocyte and CD4/CD8. These difference were statistically significant (P<0.05). Serum IFN-γ, IFN-α and FLT-3L levels were significantly higher in the HBsAg-negative group than in the HBsAg-positive group (P<0.05). However, levels of many cytokines related to inflammation (i.e., IL-6, IL-8, IL10, IL-12, IL-17A) were lower in the HBsAg-negative group. Fifty-two HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., Y100C, S114T, C124Y, P127L, G130R, T131N, M133T, C137S, G145A) and TMD region substitutions (i.e., E2K/R/D, G7D/R, G10D, A17R, F20L/S, L21V, L22V). According to the results of T-lymphocyte subsets and serum cytokines, it can be deduced that the cellular immune function of HBsAg-negative patients is superior to that of HBsAg-positive patients, with attenuation of liver inflammation. HBsAg-negative patients may show a variety of mutations and amino acid replacement sites at high frequency in the HBV S region, and these mutations may lead to undetectable HBsAg, HBsAg antigenic changes or secretion inhibition.