Journal of Interferon and Cytokine Research最新文献

COVID-19, caused by the SARS-CoV-2 virus, has caused a global health crisis, necessitating a deeper understanding of its pathophysiology. In this study, we explored the immune and hematological dynamics in COVID-19 patients to gain insights into disease severity and prognosis. Our findings revealed distinct cytokine profiles in moderate and severe cases. IL12A was significantly upregulated in peripheral blood mononuclear cells from moderate cases, suggesting a potential role in initiating an effective immune response. Conversely, severe cases exhibited downregulation of key pro-inflammatory cytokines (IL23A, TNFalpha, IL1B, and IFNG) alongside an upregulation of the immunosuppressive IL10, indicative of a dysregulated immune environment. Serum analysis showed elevated IL6 and IL10 levels in both moderate and severe cases, emphasizing their potential as markers for disease severity. Notably, no significant differences in serum cytokines were found between recovery and lethal cases. In lethal cases of COVID-19, elevated D-dimer, urea, and creatinine correlated with IL6 and IL10. This study contributes valuable information to the ongoing efforts to understand and manage the dysregulated immune responses underlying COVID-19 pathology.

India saw a spike in COVID-19 cases in early 2023, and this wave of infection was attributed to XBB sublineages of SARS-CoV-2 Omicron variant. The impact of XBB wave was significantly shorter with low burden of severe cases or hospitalization as compared with previous SARS-CoV-2 variants of concern. Although a combination of old and new mutations in the spike region of XBB.1.16 variant led to a drastic reduction in the ability of antibodies from prior immunity to neutralize this virus, additional nonspike mutations suggested a possible change in its ability to suppress innate immune responses. In this study, we tested the sensitivity of Delta, BA.2.75, and XBB.1.16 variants to interferon-β (IFN-β) treatment and found that XBB.1.16 variant was most sensitive to IFN-β. We next tested the ability of serum antibodies from healthy individuals to neutralize XBB.1.16. We showed that most of the individuals with hybrid immunity maintained a low but significant level of neutralizing antibodies to XBB.1.16 variant. Therefore, our observations indicated that both hybrid immunity because of natural infection and enhanced sensitivity to IFNs may have contributed to the low impact of XBB.1.16 infections in India.

This pilot study aimed to evaluate the immunomodulatory effect of placental mesenchymal stem/stromal cells (MSCs) on peripheral blood mononuclear cells (PBMCs) from patients with hidradenitis suppurativa (HS). Blood samples were collected from 3 healthy and 3 patients with HS. Isolated PBMCs were stained with carboxyfluorescein succinimidyl ester (CFSE) and stimulated with phorbol 12-myristate 13-acetate (PMA)/Ionomycin solution. The PBMCs of patients with HS were co-cultured with naïve MSCs (n-MSCs), activated with tumor necrosis factor (TNF)-α (10 ng/mL) and interferon (IFN)-γ (10 ng/mL) MSCs (a-MSCs), or adalimumab (30 μg/mL). The division index (proliferation inhibition) of PBMCs was analyzed by flow cytometry using the Proliferation Modeling tool after 5 days of coculture. The relative inflammatory gene expression dynamics and cytokine secretion were quantified in triplicate using real-time polymerase chain reaction (PCR) and Luminex assays. PBMCs from the HS control group showed statistically significant increases in interleukin (IL)-6 and IFN-γ cytokine concentrations and IL-17A gene expression when compared with healthy subjects. Statistically significant reduction of the division index was found in the a-MSCs group (P = 0.04). Also, the Luminex assay revealed significantly reduced proinflammatory cytokine concentrations of IL-9 (P = 0.022) and IL-17A (P = 0.022) in the a-MSCs group with the same trend of numerical lowering in n-MSCs group when compared to HS control. The results of real-time PCR revealed a numerical increase in the expression of the IL-1β, IL-36α, and TNF-α genes in both the a-MSCs and n-MSCs groups compared with the HS control. In conclusion, our findings suggest that MSCs can effectively curb PBMCs proliferation and suppress the production of inflammatory cytokines. Moreover, the preactivation of MSCs with IFN-γ and TNF-α before use can enhance their therapeutic effectiveness. Nevertheless, a larger sample size is imperative to validate these results.

Obstructive sleep apnea (OSA) is a chronic inflammatory disease characterized by partial or complete upper airway obstruction during sleep. We aimed to evaluate serum/plasma levels of several cytokines (interleukin [IL]-6, IL-12, IL-17, IL-18, and IL-23) in a systematic review meta-analysis in both adults and children with OSA compared with controls. We conducted a comprehensive search of 4 digital databases (PubMed, Web of Science, Scopus, and Cochrane Library) up until October 19, 2023, without any limitations. For our meta-analysis, we used Review Manager, version 5.3, and displayed the data as the standardized mean difference (SMD) and 95% confidence interval (CI) to assess the correlation between cytokine levels and OSA. We utilized Comprehensive Meta-Analysis version 3.0 software to conduct bias analyses, meta-regression, and sensitivity analyses. From 1881 records, 84 articles were included in the systematic review and meta-analysis. In adults, the pooled SMDs for IL-6 level were 0.79 (P value < 0.00001), for IL-17 level were 0.74 (P value = 0.14), and for IL-18 level were 0.43 (P value = 0.00002). In children, the pooled SMD for IL-6 was 1.10 (P value < 0.00001), for IL-12 was 0.47 (P value = 0.10), for IL-17 was 2.21 (a P value = 0.24), for IL-18 was 0.19 (P value = 0.07), and for IL-23 was 2.46 (P value < 0.0001). The subgroup analysis showed that the ethnicity, mean body mass index, and mean apnea-hypopnea index for IL-6 levels in adults and the ethnicity for IL-6 levels in children were effective factors in the pooled SMD. The findings of the trial sequential analysis revealed that adequate evidence has been obtained. The analysis of IL levels in adults and children with OSA compared with those without OSA revealed significant differences. In adults, IL-6 and IL-18 levels were significantly higher in the OSA group, while in children, only IL-6 and IL-23 levels were significantly elevated.

As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.

Cell-mediated immune response is critical for Mycobacterium tuberculosis (M.tb) control. Understanding of pathophysiology and role played by different cell mediators is essential for vaccine development and better management of patients with M.tb. A complex array of cytokines and chemokines are involved in the immune response against M.tb; however, their relative contribution in protection remains to be further explored. The purpose of this review is to summarize the current understanding regarding the cytokine and chemokine profiles in M.tb infection in order to assist research in the field to pursue new direction in prevention and control. We have also summarized recent findings on vaccine trials that have been developed and or are under trials that are targeting these molecules.

The recombinant human interferon alpha-2b (IFN-α2b) nasal drop formulation (Nasalferon) was studied as prophylaxis for SARS-CoV-2. Healthy volunteers between 19 and 80 years of age received 0.5 million international units of IFN in one drop (0.05 mL ) in each nostril, twice a day, for 10 consecutive days. The nondetection of SARS-CoV-2 by real-time polymerase chain reaction was the primary outcome variable. Several IFN-α biomarkers, including intranasal gene expression and innate immune effector activity, were increased in participants who received intranasal IFN-α2b. The study included 2,930 international travelers and 5,728 persons who were their close contacts. The subjects were treated with Nasalferon in January 2021, and 9,162 untreated travelers were included as controls. COVID-19 rate in treated subjects was significantly lower than in untreated subjects (0.05% vs. 4.84%). The proportion of travelers with COVID-19 decreased from 60.9% to 2.2% between December 2020 and February 2021. Furthermore, 1,719 tourism workers also received Nasalferon, and no cases of SARS-CoV-2 infection were detected, whereas 39 COVID-19 cases (10.6%) were reported in 367 untreated subjects. The main adverse events associated with the use of intranasal IFN-α2b were nasal congestion, headache, and rhinorrhea. Our prophylactic health interventions study demonstrates that the daily administration of Nasalferon for 10 days decreases the risk of developing COVID-19 in healthy volunteers. [Figure: see text].