Journal of Interferon and Cytokine Research最新文献

Interleukin-7 (IL-7) is essential for maintaining the immune system's defense functions by regulating the development and homeostasis of lymphocytes. Findings have shown the high efficacy of IL-7/IL-7 receptor (IL-7R)-based immunotherapy on various malignancies, with confirmation in both animal models and humans. In recent years, the progression-free survival and overall survival of patients suffering from gliomas significantly increased by introducing C7R-expressing chimeric antigen receptor (CAR)-T cells and long-acting IL-7 agonists such as NT-I7 (rhIL-7-hyFc, Efineptakin alfa). However, the effect of IL-7-based immunotherapies on the resistance of tumor cells to chemotherapy (when used simultaneously with chemotherapy agents) is still ambiguous and requires further studies. This article first reviews the pathophysiological roles of IL-7/IL-7R in tumors, focusing on gliomas. Subsequently, it discusses the therapeutic values of IL-7/IL-7R and the recombinant derivatives in gliomas.

Rheumatoid arthritis (RA) is an inflammatory autoimmune illness affecting around 1% of the population globally. Cytokines have a crucial role in the pathogenesis of RA. The objectives of the present study were to compare the serum cytokine profiles between methotrexate (MTX)-treated and MTX-naive RA patient groups, MTX-treated RA patient group and healthy controls, and MTX-naive RA patient group and healthy controls. Enzyme linked immunosorbent assay (ELISA) kits were used to quantify the serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-17, IL-6, interferon-gamma (IFN-γ), and IL-10 in 80 RA patients (48 MTX treated and 32 MTX naive) and 80 healthy controls. For all cytokine assays, absorbance was measured at 450 nm using a microplate reader (Bio-Rad). Independent sample t-test was used to compare the serum cytokine concentrations between the study groups using SPSS version 25. MTX-treated RA patient group had significantly reduced serum levels of TNF-α (36.13 ± 17.64 versus 45.82 ± 23.07, *P = 0.037), IL-17 (307.85 ± 151.74 versus 435.42 ± 241.19, **P = 0.006), and IFN-γ (414.93 ± 212.13 versus 527.15 ± 269.61, *P = 0.041) compared to MTX-naive RA patients. Both MTX-treated and MTX-naive RA patient groups had significantly high serum levels of TNF-α, IL-1β, IL-17, IL-6, IFN-γ, and IL-10 when compared to healthy controls (***P < 0.001). Downregulation of the serum concentrations of certain key cytokines, viz. TNF-α, IL-17, and IFN-γ, demonstrates the anti-inflammatory effect of MTX in RA patients.

Cardiac surgery can provoke an acute cytokine storm that may contribute to the development of postoperative multiple organ dysfunction syndrome. We prospectively observed patients undergoing cardiac surgery and divided them into two groups: the severe group and the mild group. Healthy individuals were enrolled acting as the control group for comparison. Plasma samples and clinical data were recorded at the initiation of cardiac-pulmonary bypass (CPB) and 3, 6, 12, 24, and 48 h after initiation of CPB. Cytokine levels were detected using the Luminex^® technique. Thirty-nine adults were enrolled in this study (14 in the severe group, 15 in the mild group, and 10 in the control group). Cytokine concentrations were significantly higher in the severe group. Principal component analysis was used to establish a cytokine storm intensity curve, which represented the overall trend of 10 cytokines. The peak concentrations of interleukin (IL)-6, IL-10, and IL-16 were 425.1, 198.5, and 623.0 pg/mL, which were more than 1,200, 1,800, and 240 times the normal level, respectively. The maximum cytokine storm intensity predated the maximum Vasoactive-Inotropic Score (VIS) and Sequential Organ Failure Assessment (SOFA) score in the severe group. Cytokine storm response to cardiac surgery occurred early and was associated with disease severity. Interventions to cytokine storm should be initiated early as guided by cytokine storm biomarkers such as IL-6, IL-10, and IL-16 in severe patients undergoing cardiac surgery. Clinical Trial Registration: ChiCTR1900021351.

Osteosarcoma is the most prevalent type of primary bone malignancy in children and adolescents. The effect of cytokines on osteosarcoma prognosis has been studied and reported. This meta-analysis aimed to assess the prognostic value of cytokines as osteosarcoma biomarkers. Databases including PubMed, Embase, and Cochrane Library were searched for studies on the prognostic value of cytokines in osteosarcoma. From the eligible studies, data on overall survival (OS), disease-free survival, and metastasis-free survival (MFS) were extracted. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. A total of 11 studies involving 755 patients were included in this analysis. High macrophage migration inhibitory factor (MIF) expression in tumors was significantly associated with shortened OS (HR = 2.01, 95% CI: 1.18-3.42, P = 0.010) and MFS (HR = 2.51, 95% CI: 1.47-4.01, P = 0.001). Elevated T cell immunoglobulin and mucin domain-3 (Tim-3) levels in serum correlated with increased risk of disease progression in patients with osteosarcoma (HR = 3.14, 95% CI: 2.88-3.03, P < 0.001). However, interleukin 6 (IL-6) and tumor necrosis factor were not substantially associated with osteosarcoma prognosis. Owing to a paucity of research, other relevant cytokines [interferon-α/β receptor, tissue factor, macrophage inhibitory cytokine 1 (MIC-1), and IL-23] could not be combined. In conclusion, MIF levels in tumors and Tim-3 levels in serum can be potential biomarkers of poor prognosis in osteosarcoma. To confirm this finding and implement these biomarkers into clinical applications, additional large-scale, high-quality studies are needed.

Diet-induced obesity triggers elevation of circulating pro-inflammatory cytokines and acute-phase proteins, including interferons (IFNs). IFNs strongly contribute to low-grade inflammation associated with obesity-related complications, such as nonalcoholic fat liver disease and diabetes. In this study, AG129 mice model (double-knockout strain for IFN α/β/γ receptors) was fed with a high-fat high-sucrose (HFHS) diet (Western diet) for 20 weeks aiming to understand the impact of IFN receptor ablation on diet-induced obesity, insulin resistance, and nonalcoholic fat liver disease. Mice were responsive to the diet, becoming obese after 20 weeks of HFHS diet which was accompanied by 2-fold increase of white adipose tissues. Moreover, animals developed glucose and insulin intolerance, as well as dysregulation of insulin signaling mediators such as Insulin Receptor Substrate 1 (IRS1), protein kinase B (AKT), and S6 ribosomal protein. Liver increased interstitial cells, and lipid accumulation was also found, presenting augmented fibrotic markers (transforming growth factor beta 1 [Tgfb1], Keratin 18 [Krt18], Vimentin [Vim]), yet lower expression on IFN receptor downstream proteins (Toll-like receptor [TLR] 4, nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB], and cAMP response element-binding protein [CREB]). Thus, IFN receptor ablation promoted effects on NFκB and CREB pathways, with no positive effects on systemic homeostasis in diet-induced obese mice. Therefore, we conclude that IFN receptor signaling is not essential for promoting the complications of diet-induced obesity and thus cannot be correlated with metabolic diseases in a noninfectious condition.

Neurologic manifestations of postacute sequelae after SARS-CoV-2 infection (neuro-PASC) are common; however, the underlying drivers of those symptoms remain poorly understood. Prior work has postulated that immune dysregulation leads to ongoing neuroinflammation. We aimed to identify the cytokines involved in that immune dysregulation by comparing 37 plasma cytokine profiles among 20 case patients with neuro-PASC to 20 age- and gender-matched controls. Neuro-PASC cases were defined as individuals with self-reported persistent headache, general malaise, and anosmia or ageusia at least 28 days post-SARS-CoV-2 infection. As a sensitivity analysis, we repeated the main analysis among only participants of Hispanic heritage. In total, 40 specimens were tested. Participants were an average of 43.5 years old (interquartile range 30-52), 20 (50.0%) of whom identified as women. Levels of tumor necrosis factor alpha (TNFα) were 0.76 times lower [95% confidence interval (CI) 0.62-0.94] among cases of neuro-PASC compared with controls, as were levels of C-C motif chemokine 19 (CCL19) (0.67; 95% CI 0.50-0.91), C-C motif chemokine 2 (CCL2) (0.72; 95% CI 0.55-0.95), chemokine interferon-gamma inducible protein 10 (CXCL10) (0.63; 95% CI 0.42-0.96), and chemokine interferon-gamma inducible protein 9 (CXCL9) (0.62; 95% CI 0.38-0.99). Restricting analysis of TNF and CCL19 to participants who identified as Hispanic did not alter results. We noted a reduction in TNFα and down-stream chemokines among patients with neuro-PASC, suggesting an overall immune attenuation.

Angiogenesis, retinal neuropathy, and inflammation are the main molecular features of diabetic retinopathy (DR) and should be taken into consideration for potential treatment approaches. Retinal pigmented epithelial (RPE) cells play a major role in DR progression. This study evaluated the in vitro effect of interferon (IFN) α-2b on the expression of genes involved in apoptosis, inflammation, neuroprotection, and angiogenesis in RPE cells. RPE cells were cocultured with IFN α-2b at 2 doses (500 and 1,000 IU) and treatment periods (24 and 48 h). The quantitative relative expression of genes (BCL-2, BAX, BDNF, VEGF, and IL-1b) was evaluated in the treated versus control cells through real-time polymerase chain reaction (PCR). The result of this study demonstrated that IFN treatment at 1,000 IU (48 h) led to significant upregulation of BCL-2, BAX, BDNF, and IL-1b; however, the BCL-2/BAX ratio was not statistically altered from 1:1, in any of the treatment patterns. We also showed that VEGF expression was downregulated in RPE cells treated with 500 IU for 24 h. It can be concluded that IFN α-2b was safe (BCL-2/BAX ∼1:1) and enhanced neuroprotection at 1,000 IU (48 h); however-at the same time-IFN α-2b induced inflammation in RPE cells. Moreover, the antiangiogenic effect of IFN α-2b was solely observed in RPE cells treated with 500 IU (24 h). It seems that IFN α-2b in lower doses and short duration exerts antiangiogenic effects and in higher doses and longer duration has neuroprotective and inflammatory effects. Hence, appropriate concentration and duration of treatment, according to the type and stage of the disease, should be considered to achieve success in IFN therapy.