Objective To identify the effects of single immunoglobin IL-1 receptor related protein （SIGIRR） on inflammation induced by high mobility group box 1 （HMGB1） in A549 derived from human alveolar epithelial cells. Methods Eukaryotic expression vectors pCDNA3.1（+） constructed with SIGIRR cDNA were transiently transfected into A549 cells，in which SIGIRR was forced to be over-expressed. Western blot and RT-PCR were applied to detect the expression level of SIGIRR after transfection. After the stimulation by HMGB1，the transcriptional activity of NF-κB in A549 cells was detected by dual-luciferase reporter assay system，and the protein levels of inflammatory cytokine TNF-α and IL-1β were measured by ELISA. Results The expression level of SIGIRR increased significantly in A549 cells transfected with SIGIRR vectors. The transcriptional activity of NF-κB was enhanced obviously after HMGB1 treatment in A549 cells by dual-luciferase reporter assay system，while the transfection of SIGIRR vectors decreased the activity. The protein levels of TNF-α and IL-1β were down-regulated in A549 cells over-expressing SIGIRR after HMGB1 stimulation compared with the non-transfected cells. Conclusions Up-regulated SIGIRR expression can inhibit HMGB1-induced proinlammatory cytokine release in A549 cells such as TNF-α and IL-1β. The transcriptional activity of NF-κB is dampened by SIGIRR transfection，implying that the anti-inflammatory effects of SIGIRR may be involved in the regulation of NF-κB.
Intraocular lymphoma (IOL) is a rare lymphocytic malignancy. The gold standard for the definite diagnosis remains histopathologic examination of the ocular specimen. But cytologic confirmation of malignant lymphoma cells in vitreous or chorioretinal specimens is challenging and dependending on highly skilled cytopathologist, due to the sparse cellularity and specimen degeneration. Consequently, false-negative rates arecommon, which delays diagnosis and treatment seriously. Because of the limited diagnostic capacity of cytology, other adjunct diagnostic tools have been developed. Additional procedures that may support IOL diagnosis include flow cytometry, immunocytochemistry, cytokines study with identification of interleukin (IL)-10 and IL-6 level, and polymerase chain reaction amplification. And more recently, new techniques of mutational analysis have been validated for the diagnosis of vitreoretinal lymphoma (VRL) and may represent a helpful diagnostic tool for the detection of early cases. Metagenomic deep sequencing technology may provide an important basis for VRL diagnosis and personalized treatment. In the future, it is expected to deepen the understanding of IOL disease phenotypes at the molecular level, discover new target therapies, monitor response to treatment, and detect intraocular recurrences. These may offer insights into how we might create a tailored therapeutic approach for each patient's VRL in the future.
ObjectiveTo summarize the research status and progress of interleukin-6 (IL-6) in Takayasu arteritis (TAK). MethodRecent literature published at home and abroad about the study of IL-6 in the TAK was reviewed and analyzed. ResultsIL-6 was a pro-inflammatory cytokine secreted by a variety of cells, which participated in a variety of inflammatory and immune reactions, and played an important role in the progress of TAK. The expression levels of IL-6 in the peripheral blood and vascular wall tissues of patients with TAK were increased. The gene polymorphism of IL-6 might be related to the occurrence of TAK. Tocilizumab, an IL-6 receptor antagonist, was effective and safe in the treatment of TAK. ConclusionsIL-6 can be used as one of the monitoring indicators for the active phase and recurrence of TAK. IL-6 receptor antagonist can be used as the treatment choice of TAK, but the application results in different stages of TAK are still worth expecting.
Patients with coronavirus disease 2019 may have systemic symptoms of varying degrees. These symptoms are related to inflammatory response, massive release of pro-inflammatory cytokines and cytokine storm. In recent years, programmed necrosis, as a controllable type of necrosis, is considered to be an important factor that mediates inflammation. Recent studies have shown that programmed necrosis is involved in the inflammatory response and pulmonary fibrosis of coronavirus disease 2019. This article mainly reviews the mechanism of programmed necrosis, its participation in the occurrence and development of coronavirus disease 2019, and the research progress of programmed necrosis inhibitors in the treatment of coronavirus disease 2019, aiming to provide a certain basis for the diagnosis and treatment of coronavirus disease 2019.
Objective To observe the expression and investigate the significance of suppressor of cytokine signaling (SOCS) in peripheral blood mononuclear cells (PBMC) of experimental autoimmune uveitis (EAU). Methods 100 Lewis rats were immunized with interphotoreceptor retinoid-binding protein (IRBP) to induce EAU animal model, and they were divided into control group and treatment group randomly. The treatment group was administered cyclosporine A 20mg/（kgmiddot;d）after 1 to 28 days of immunization; the control group received saline buffer at equal quantity. All eyes were evaluated by slit-lamp microscopy before and after 7, 14, 21, 28 days of immunization; IL-4，IL-12，IFN-gamma; in the serum were measured by enzyme linked immunosorbent assay(ELISA); the SOCS mRNA and protein level in PBMC were measured by quantitative polymerase chain reaction (q-PCR) and western blot. Results The inflammation was most obvious at 14 days after immunization. The control group showed obvious iridocyclitis; the treatment group showed mild anterior chamber inflammation but no posterior synechia and hypopyon. The highest level of IL-12 and IFN-gamma; were observed at 14 days after immunization, followed by decline to the baseline at 28 days after immunization in control group; the highest level of IL-12 and IFN-gamma; were found at 14 days after immunization in treatment group, but the level was lower than control group obviously. Compared with the level before immunization, there are no differences at other time-point. The concentration of IL-4 decreased indistinctly in control group but increased in treatment group. SOCS1、Both of SOCS1 and SOCS5 increased to the highest level at 14 days after immunization, as 4.05 and 383 times of preimmunization in control group respectively, as 1.15 and 1.16 times in treatment group respectively. The CIS and SOCS3 mRNA increased lightly in two groups and treatment group milder than control group. Marked increased expression of SOCS1 and SOCS5 protein was detected at 7, 14, 21days than preimmunization, both of CIS and SOCS3 protein were significantly increased on 14, 21 days in control group; only SOCS1 protein was significantly increased on 14 days in treatment group and there are no differences at other time-point compared to pre-immunization. Conclusion Up-regulation of SOCS1 and SOCS5 expression maybe related to intensive response of Th1 in the development of EAU. Mild up-regulation of CIS and SOCS3 maybe associated with intensive response of Th2 which against the reaction of Th1 to carry out the dynamic immune balance.
ObjectiveTo improve clinicians' understanding of severe cytokine release syndrome (CRS) through reporting the clinical manifestation, diagnosis, treatment, and prognosis of CRS after chimeric antigen receptor T (CAR-T) cell therapy in a patient with solid tumor. Methods A patient with ovarian cancer who suffered severe CRS after CAR-T cell therapy in the Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University was reviewed. Relevant studies were searched for literature review. Results The patient, a 55-year-old woman, was diagnosed with ovarian cancer in early 2016 and continued to progress despite multiple lines of treatment, so she received CAR-T cell therapy on September 16, 2022. The patient developed a fever 2 days after infusion, and developed dyspnea and shortness of breath with oxygen desaturation 2 days later. Her condition kept deteriorating with respiratory distress and severe hypoxia 6 days after infusion, and the level of interleukin-6 and interferon-gamma continued to be elevated. Chest CT showed pleural effusion and massive exudation of both lungs. Considered to have acute respiratory distress syndrome (ARDS) due to severe CRS, she was transferred to the intensive care unit (ICU). The patient was treated with tocilizumab, high-dose intravenous glucocorticoid pulses, mechanical ventilation, and sivelestat sodium for ARDS. Her symptoms were gradually relieved, and the results of laboratory tests were gradually stabilized. The patient was extubated 6 days after ICU admission and discharged from ICU a week later. Six patients were screened out with ARDS or acute respiratory failure caused by CRS after CAR-T cell therapy, whose treatments were mainly anticytokine agents combined with high-flow oxygen therapy or invasive mechanical ventilation. One of them died. ConclusionsClinicians should be alert to severe CRS during the administration of CAR-T cell. Rapid interruption of the inflammation development is the key to all treatments. If respiratory and/or circulatory dysfunction occurs, patients should be transferred to ICU in time for organ support therapy.
Cytokine storm is a life-threatening hyperinflammatory response. Current limited evidence-based research findings suggest that cytokine adsorption technologies do not reduce mortality in patients undergoing cardiac surgery or those with septic shock, nor do they improve hemodynamics or lower interleukin-6 levels. These negative outcomes may be related to improper timing and method of use, insufficient adsorption efficacy and non-specific adsorption of antibiotics, albumin, platelets, and other substances. This article summarizes the optimal timing for initiating and terminating cytokine adsorption therapy, treatment modality selection, as well as treatment duration and frequency, aiming to provide clinical guidance.
Tree shrew is a novel and high-quality experimental animal model. In this study, the real-time polymerase chain reaction methods were established to detect infection-related cytokines interleukin-6 (IL-6), IL-8, IL-10, IL-17A, interferon-γ (IFN-γ) and housekeeping gene glyceraldehyde-phosphate dehydrogenase (GAPDH) of tree shrew. The results indicated that the establised methods had good specificity. The high point of the linear range of these reagents reached 1 × 1010 copies, and the low points ranged from 10 copies (IL-6, IL-17A), 100 copies (IL-10, GAPDH) to 1 000 copies (IL-8, IFN-γ). In this interval, the linear correlation coefficient R2 of each reagent was greater than 0.99. The lowest detectable values of IL-6, IL-8, IL-10, IL-17A, IFN-γ and GAPDH were 8, 8, 4, 8, 128 and 4 copies, respectively. The results showed that the established detection methods had good specificity, sensitivity and wide linear range. The methods were suitable for detection of multiple concentration range samples, and could be used for the subsequent studies of tree shrew cytokines.
Objective To explore the effect of IL-10 on the inhibition of early proinflammatory cytokine release in intraabdominal infection and early sepsis. Methods Forty eight SD rats were randomized into 4 groups, 12 in each group, ①sham operation group, ②control group, ③prophylactic group, ④therapeutic group. Group 1 underwent laparotomy only, group 2 received laparotomy and cecal ligation plus punctures (CLP) with saline injected once every 3 hrs, group 3 underwent CLP and IL-10 injection intraperitoneally 1 hr before surgery and once every 3 hrs following operation, group 4 received CLP and IL-10 injection once every 3 hrs after operation. At 3 and 9 hr points, rats were sacrificed and blood samples were taken for measurement of inflammatory cytokines. Results Almost no inflammatory cytokines were detected in sham group, CLP produced a significant rise in serum TNF-α (tumor necrosis α), IL-1, IL-6 (interleukin 1,6) in control group, IL-10 reduced the rise of inflammatory cytokines significantly. Conclusion IL-10 could inhibit the early inflammatory cytokine release in rat model of sepsis. Suggesting it may attenuate the severity of inflammation.
ObjectiveTo investigate the effect of etomidate and propofol on inflammatory cytokines and cortisol for patients with lung adenocarcinoma. MethodSixty patients scheduled for lung cancer surgery under general anesthesia were studied. All patients were randomly divided into an etomidate total intravenous anesthesia group (group E, 30 patients, 16 males and 14 females at age of 58.0±5.0 years) and a propofol total intravenous anesthesia group (group P, 30 patients, 17 males and 13 females at age of 55.0±5.0 years), with 30 patients in each group. ResultsThe concentration of IL-6 in serum of patients in the two groups at time points T1, T2 and T3 was significantly higher than those at time point T0 (P < 0.01). The concentration of IL-10 and TNF-α in serum of patients at time points T1 and T2 was significantly higher than those at time point T0 (P < 0.01). And the difference of the concentration of TNF-α in serum of patients at time points T0 and T3 was not statistically significant (P > 0.05). The level of Cor of patients in the group E at time point T0 was slightly higher than those at time point T1, but lower than that at time points T2 and T3. There was no statistical difference in the concentration of IL-6 and TNF-α in serum of patients between the two groups. The level of IL-10 of patients in the group E at time points T2 and T3 was lower than those in the group P (P < 0.05), but no significant difference was observed at the other time points. The concentration of Cor in the patients in the group E at time point T1 was lower than that in the group P (P < 0.01), but no significant difference was observed either at the other time points. ConclusionThe effect of etomidate used for maintenance of general anesthesia on the inflammatory factors is essentially similar to that of propofol.