Objective To investigate the expressions of IL-18,IL-18 binding protein isoform a(IL-18BPa)and IL-18Rα in blood CD4+Th1 cells of patients with allergic asthma(AA),and with allergic rhinitis and asthma syndrome(ARA),and the effects of allergens on their expressions.Methods Blood samples were collected from patients with AA,ARA and healthy control(HC)subjects.Flow cytometry was used to evaluate the actions of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα in CD4+Th1 cells.Ovalbumin(OVA)-induced AA mouse models were established,and the expression level of IL-18Rα along with the influence of IL-18 on its expression in blood and lung Th1 cells was also explored by flow cytometry.Results Compared with HC,we observed increased IL-18 while decreased IL-18BPa expression in blood Th1 cells of AA and ARA patients.Moreover,allergens upregulated the expression levels of IL-18,IL-18BPa and IL-18Rα in Th1 cells of patients with AA and ARA.Additionally,intratracheal challenge with OVA plus IL-18 increased the proportions of blood and lung Th1 cells of HC and AA mice,and upregulated IL-18Rα expression on blood and lung Th1 cells of HC mice.Conclusion Allergens may be involved in the pathogenesis of airway allergic diseases by inducing the expressions of IL-18 and IL-18Rα in CD4+Th1 cells.

Allergic rhinitis(AR)is the most common airway allergic diseases.Basophils are the classical effector cells in allergy,including AR:Both IgE and non-IgE mediated methods can activate basophils during allergic reactions and induce basophils to release various inflammatory mediators,which is accompanied by changes in the expression of multiple membrane proteins,and ulti-mately leading to the clinical manifestations of allergic diseases.IL-18 may be involved in the pathogenesis of AR by directly inducing basophil activation and inflammation response via binding to its receptor IL-18Rα.Nevertheless,the binding of IL-37b to IL-18Rα initiates the downstream anti-inflammatory signals,thus inhibiting inflammation reaction in AR.Therefore,understanding the role and mechanism of IL-18 and IL-37b in the activation of blood basophils of AR patients is of great significance for the pathogenesis,treat-ment of AR and the development of related biological agents.

Objective:To investigate the effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in blood CD4+Th17 cells of patients with allergic rhinitis and asthma syndrome(ARA)and plasma levels of IL-17A and IL-17F in ARA patients.Methods:ARA patients(n=25)and healthy volunteers(n=22)in the First Affiliated Hospital of Jinzhou Medical University and Henan Provincial People's Hospital were recruited,and blood samples of the subjects were collected.Proportions of CD4+Th17 cells,and effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in Th17 cells were determined by flow cytometry.Levels of IL-17A and IL-17F were examined by Bioplex system.Correlation between levels of free plasma free IL-18(fIL-18)and IL-17A,and per-centage of Th17 cells was further analyzed.Results:Proportion of IL-18+cells in Th17 cells was increased in ARA patients by 26.0%(P<0.01),and house dust mite allergen induced 1.22-fold elevation in expression of IL-18 in Th17 cells(P<0.05).In addition,Arte-misiae sieversiana wild pollen allergen enhanced expressions of IL-18 and IL-18Rα in Th17 cells of ARA patients(P<0.05).Plasma levels of IL-17A and IL-17F were increased by 2.2 and 1.1 folds,respectively(P<0.05)in ARA patients,and they correlated well with other(R=0.712,P<0.01).Moreover,the increased level of fIL-18 was moderately correlated with the increased level of IL-17A and the elevated proportion of Th17 cells in ARA patients(r=0.607,r=0.652,P<0.05).Conclusion:The increased plasma fIL-18 in ARA patients may be derived from Th17 cells.Allergens may be involved in pathogenesis of ARA by inducing elevated IL-18 and IL-18Rα expressions in Th17 cells.

Objective:To investigate the effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in blood CD4+Th17 cells of patients with allergic rhinitis and asthma syndrome(ARA)and plasma levels of IL-17A and IL-17F in ARA patients.Methods:ARA patients(n=25)and healthy volunteers(n=22)in the First Affiliated Hospital of Jinzhou Medical University and Henan Provincial People's Hospital were recruited,and blood samples of the subjects were collected.Proportions of CD4+Th17 cells,and effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in Th17 cells were determined by flow cytometry.Levels of IL-17A and IL-17F were examined by Bioplex system.Correlation between levels of free plasma free IL-18(fIL-18)and IL-17A,and per-centage of Th17 cells was further analyzed.Results:Proportion of IL-18+cells in Th17 cells was increased in ARA patients by 26.0%(P<0.01),and house dust mite allergen induced 1.22-fold elevation in expression of IL-18 in Th17 cells(P<0.05).In addition,Arte-misiae sieversiana wild pollen allergen enhanced expressions of IL-18 and IL-18Rα in Th17 cells of ARA patients(P<0.05).Plasma levels of IL-17A and IL-17F were increased by 2.2 and 1.1 folds,respectively(P<0.05)in ARA patients,and they correlated well with other(R=0.712,P<0.01).Moreover,the increased level of fIL-18 was moderately correlated with the increased level of IL-17A and the elevated proportion of Th17 cells in ARA patients(r=0.607,r=0.652,P<0.05).Conclusion:The increased plasma fIL-18 in ARA patients may be derived from Th17 cells.Allergens may be involved in pathogenesis of ARA by inducing elevated IL-18 and IL-18Rα expressions in Th17 cells.

Interleukin-18 (IL-18) and IL-37b have recently become a research hotspot because of their biological antagonistic role in inflammatory response. Sepsis is an abnormal inflammatory response-mediated life-threatening organ dysfunction induced by infection. Septic shock is the most severe form of sepsis, and has attracted great attention in clinical research due to its high mortality. Basophils are one of the classical effector cells in the inflammatory response, which are involved in many aspects of the pathological process of sepsis. IL-18 is an important pro-inflammatory cytokine and plays a key role in the inflammatory response, while IL-37b is known for its anti-inflammatory function. Both IL-18 and IL-37b can regulate the function of basophils and the inflammatory response in sepsis reversely through interleukin-18 receptor α (IL-18Rα). Therefore, it is of great clinical significance to investigate the role and mechanism of IL-18, IL-37b and basophils in the pathogenesis of sepsis. Herein, the relevant literatures on the roles and potential mechanisms of IL-18, IL-37b and basophils in the pathogenesis of sepsis are summarized, aiming to provide theoretical basis and novel ideas for the future research on the potential roles of IL-18, IL-37b and basophils in sepsis.
Humans ; Sepsis/immunology* ; Basophils/immunology* ; Interleukin-18/metabolism* ; Interleukin-1/metabolism* ; Animals

Objective To investigate the expressions of IL-18,IL-18 binding protein isoform a(IL-18BPa)and IL-18Rα in blood CD4+Th1 cells of patients with allergic asthma(AA),and with allergic rhinitis and asthma syndrome(ARA),and the effects of allergens on their expressions.Methods Blood samples were collected from patients with AA,ARA and healthy control(HC)subjects.Flow cytometry was used to evaluate the actions of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα in CD4+Th1 cells.Ovalbumin(OVA)-induced AA mouse models were established,and the expression level of IL-18Rα along with the influence of IL-18 on its expression in blood and lung Th1 cells was also explored by flow cytometry.Results Compared with HC,we observed increased IL-18 while decreased IL-18BPa expression in blood Th1 cells of AA and ARA patients.Moreover,allergens upregulated the expression levels of IL-18,IL-18BPa and IL-18Rα in Th1 cells of patients with AA and ARA.Additionally,intratracheal challenge with OVA plus IL-18 increased the proportions of blood and lung Th1 cells of HC and AA mice,and upregulated IL-18Rα expression on blood and lung Th1 cells of HC mice.Conclusion Allergens may be involved in the pathogenesis of airway allergic diseases by inducing the expressions of IL-18 and IL-18Rα in CD4+Th1 cells.

Objective:To compare the degranulation levels of basophils in peripheral blood mononuclear cell (PBMC) and granulocyte populations between healthy subjects and patients with sepsis, and to explore the underlying mechanisms. Additionally, plasma cytokine levels were measured in these volunteers.Methods:Peripheral blood samples were collected from both healthy individuals and sepsis patients. The degranulation level of basophils in sepsis patients and its potential mechanisms were examined. Plasma levels of IL-1β, IL-9, and IL-10 were detected, and Pearson correlation analysis was performed to assess the relationship between degranulated basophils in the granulocyte population and IL-9 levels.Results:Compared with healthy subjects, sepsis patients showed a reduction in basophil percentages within PBMC and granulocyte populations by 94.8% and 37.9%, respectively ( Z = -6.441, P < 0.05; Z = -2.681, P < 0.05). In contrast, both the proportion and number of degranulated basophils in the granulocyte population were increased (both P < 0.05). Plasma levels of IL-1β, IL-9, and IL-10 were significantly elevated in sepsis patients--by 80.6%, 36.7%, and 11.9-fold, respectively ( Z = -4.258, P < 0.05; Z = -3.606, P < 0.05; Z = -4.814, P < 0.05). Moreover, plasma IL-9 levels were highly correlated with both the percentage and count of degranulated basophils in the granulocyte population (both P < 0.05). GO and KEGG enrichment analyses revealed cytological changes and potential mechanisms involving basophils in the PBMC of sepsis patients. Conclusions:The decreased total count of basophils in sepsis patients may elevate the risk of secondary infection. Degranulated basophils in the granulocyte population may contribute to excessive inflammatory responses through IL-9 secretion.

Allergic rhinitis(AR)is the most common airway allergic diseases.Basophils are the classical effector cells in allergy,including AR:Both IgE and non-IgE mediated methods can activate basophils during allergic reactions and induce basophils to release various inflammatory mediators,which is accompanied by changes in the expression of multiple membrane proteins,and ulti-mately leading to the clinical manifestations of allergic diseases.IL-18 may be involved in the pathogenesis of AR by directly inducing basophil activation and inflammation response via binding to its receptor IL-18Rα.Nevertheless,the binding of IL-37b to IL-18Rα initiates the downstream anti-inflammatory signals,thus inhibiting inflammation reaction in AR.Therefore,understanding the role and mechanism of IL-18 and IL-37b in the activation of blood basophils of AR patients is of great significance for the pathogenesis,treat-ment of AR and the development of related biological agents.

Objective:To investigate the expression of IL-18, IL-18-binding protein a(IL-18BPa) and IL-18 receptor α(IL-18Rα) by peripheral blood CD4 + Th17 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expression. Methods:This study enrolled 45 outpatients with AR and 23 healthy control subjects receiving physical examination in the First Affiliated Hospital of Jinzhou Medical University from October 2019 to September 2020. According to the results of skin prick test, the 45 patients were divided into two groups: AR group with positive results (24 cases) and nAR group with negative results (21 cases). Blood samples of them were collected. Flow cytometry was used to analyze the effects of allergens on the expression of IL-18, IL-18BPa and IL-18Rα at protein level by peripheral blood CD4 + Th17 cells. The level of IL-17A in plasma was measured by Bioplex system, and its correlation with the percentage of IL-18 + Th17 cells was analyzed. Results:Compared with the healthy control group, the AR group showed increased ratios of CD4 + Th17 and IL-18 + Th17 cells ( P<0.01), decreased ratio of IL-18BPa + Th17 cells ( P<0.01), enhanced mean fluorescence intensity (MFI) of IL-18BPa ( P<0.01) and reduced MFI of IL-18Rα ( P<0.01); the nAR group showed enhanced MFI of IL-18BPa ( P<0.000 1) and reduced MFI of IL-18Rα ( P<0.000 1). The ratio of IL-18 + Th17 cells and the MFI of IL-18Rα in the AR group were higher than those in the nAR group ( P<0.05, P<0.01). House dust mite extract and Platanus pollen extract induced the expression of IL-18 and IL-18BPa by CD4 + Th17 cells of AR patients ( P<0.05). Moreover, house dust mite extract directly induced the CD4 + Th17 cells isolated from the healthy control subjects to express IL-18 and IL-18R ( P<0.05). Compared with healthy control subjects, AR patients had higher level of IL-17A in plasma and it was moderately correlated with the ratio of IL-18 + Th17 cells ( P<0.05). Conclusions:Allergens may be involved in the pathogenesis of AR by inducing blood CD4 + Th17 cells to express IL-18 and IL-18Rα.

Sepsis is a life-threatening organ dysfunction,which is caused by the body's uncontrolled immune response to infection.Tissue masts cells(MC),derived from blood mast cell progenitors,are one of the classical effector cells in inflammatory response.MC plays an important role in sepsis via secreting a variety of inflammatory mediators and cytokines.Here,we summarized the potential roles of MC in sepsis,which is expected to provide novel ideas for the future research on the novel mechanisms of MC in sepsis.