“…14 Animal experiments have shown that IVIG could decrease the proinflammatory cytokines' concentrations in septic mice. 19 Data from animal inflammation models and human cells showed that IVIG could enhance the regulatory T-cell proliferation and suppress pro-inflammatory Th17 cells, 20,21 with decreased pro-inflammatory cytokines (such as IL-17A and IL-6) and increased anti-inflammatory cytokines (such as IL-10). 22,23 We also found that, after IVIG treatment, the IL-6 concentration in plasma was decreased in the COVID-19 patients (data were not shown), suggesting that the benefits by IVIG might be associated with reduced inflammation.…”
Section: Discussionmentioning
confidence: 99%
“…Immunoglobulin has been used in the treatment of viral infectious diseases, such as viral pneumonia, and autoimmune diseases 14 . Animal experiments have shown that IVIG could decrease the pro‐inflammatory cytokines’ concentrations in septic mice 19 . Data from animal inflammation models and human cells showed that IVIG could enhance the regulatory T‐cell proliferation and suppress pro‐inflammatory Th17 cells, 20,21 with decreased pro‐inflammatory cytokines (such as IL‐17A and IL‐6) and increased anti‐inflammatory cytokines (such as IL‐10) 22,23 .…”
Objective. Coronavirus disease 2019 (COVID-19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID-19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID-19 patients was lacking. Methods. 325 patients with laboratory-confirmed critical COVID-19 were enrolled from 4 government-designated COVID-19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28-and 60-day mortality, and the secondary outcomes were the total length of in-hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing. Results. In the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28-day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in-hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28-day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60-day mortality in the critical-type patients. Conclusion. Early administration of IVIG with high dose
“…14 Animal experiments have shown that IVIG could decrease the proinflammatory cytokines' concentrations in septic mice. 19 Data from animal inflammation models and human cells showed that IVIG could enhance the regulatory T-cell proliferation and suppress pro-inflammatory Th17 cells, 20,21 with decreased pro-inflammatory cytokines (such as IL-17A and IL-6) and increased anti-inflammatory cytokines (such as IL-10). 22,23 We also found that, after IVIG treatment, the IL-6 concentration in plasma was decreased in the COVID-19 patients (data were not shown), suggesting that the benefits by IVIG might be associated with reduced inflammation.…”
Section: Discussionmentioning
confidence: 99%
“…Immunoglobulin has been used in the treatment of viral infectious diseases, such as viral pneumonia, and autoimmune diseases 14 . Animal experiments have shown that IVIG could decrease the pro‐inflammatory cytokines’ concentrations in septic mice 19 . Data from animal inflammation models and human cells showed that IVIG could enhance the regulatory T‐cell proliferation and suppress pro‐inflammatory Th17 cells, 20,21 with decreased pro‐inflammatory cytokines (such as IL‐17A and IL‐6) and increased anti‐inflammatory cytokines (such as IL‐10) 22,23 .…”
Objective. Coronavirus disease 2019 (COVID-19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID-19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID-19 patients was lacking. Methods. 325 patients with laboratory-confirmed critical COVID-19 were enrolled from 4 government-designated COVID-19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28-and 60-day mortality, and the secondary outcomes were the total length of in-hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing. Results. In the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28-day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in-hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28-day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60-day mortality in the critical-type patients. Conclusion. Early administration of IVIG with high dose
“…The cecum, usually located in the right upper abdomen, was extracted using anatomical forceps. A 3–0 silk suture was passed through the mesocecum, and the cecum was ligated at its upper third adjacent to its root [ 7 ]. The cecum was then bilaterally punctured by inserting an 18-gauge needle through the cecal wall followed by cecal pressing with sterile cotton swabs and extrusion of the intestinal contents through the punctured openings.…”
Background
Intestinal obstruction can result in inflammatory injury to distant organs, especially the lungs. Stellate ganglion block (SGB) provides sympathetic nervous homeostasis and inhibits the systemic inflammatory response. This study aimed to investigate whether SGB can alleviate acute lung injury by inhibiting phospholipase A2 expression in rats.
Methods
Thirty healthy male Sprague–Dawley rats were divided into three groups: C group (sham-operated); CLP group (cecal ligation and puncture with intestinal obstruction), and cervical sympathetic trunk transection (CSTT) group (transection of the cervical sympathetic trunk following CLP).Arterial blood samples were obtained to determine the ratio of partial arterial pressure of oxygen (PaO2) to fraction of oxygen in inspired air (FiO2). Venous blood samples were used to evaluate the serum concentrations of chemokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 using enzyme-linked immunosorbent assays. Following euthanasia, the lungs were isolated to estimate the wet/dry lung weight (W/D) ratio, evaluate the pathological damage to lung tissues on microscopy, and determine secretory-type phospholipase A2 (sPLA2) expression using western blotting.
Results
Rats in the CLP group showed increased fatigue, decreased activity levels, and coarse, gray hair. The levels of chemokines, TNF-α, and IL-6 in the CLP and CSTT groups were higher than those in the C group. However, the levels were lower in the CSTT group than those in the CLP group. IL-10 levels in the CLP group were higher and lower than those in the C and CSTT groups, respectively. W/D ratios and PaO2/FiO2 in the CLP and CSTT groups were higher than those in the C group, whereas these ratios in the CSTT group were lower than those in the CLP group. No lung injury was noted in group C, and the lung injury scores were lower in the CSTT group than those in the CLP group. sPLA2 expression levels in the CLP group were higher than those in the C group, whereas these levels in the CSTT group were lower than those in the CLP group.
Conclusions
sPLA2 overexpression in the lungs may be a pathogenic factor in acute lung injury. CSTT alleviated acute lung injury by inhibiting sPLA2 expression.
“…The rationale is the ability of the immunoglobulins to (i) recognize and neutralize pathogens and associated toxins, (ii) anti-apoptotic effect on immune cells, and (iii) inhibit transcription [ 43 ]. Although the application of IVIg has been found to significantly reduce the sequential organ failure assessment scores (SOFA), apoptosis [ 44 ], and disseminated intravascular coagulation (DIC) [ 45 ] while increasing the blood level of immunoglobulins [ 46 ], it was unable to reduce mortality in sepsis patients [ 47 ]. The meta-analysis carried out by Cui and his group in 2019 revealed reduced mortality among adult patients with sepsis by intravenous administration of IgM-enriched immunoglobulin (IVIgGM).…”
Section: Current Therapeutic Approaches To Treat Sepsismentioning
Sepsis is a life-threatening condition characterized by an uncontrolled inflammatory response to an infectious agent and its antigens. Immune cell activation against the antigens causes severe distress that mediates a strong inflammatory response in vital organs. Sepsis is responsible for a high rate of morbidity and mortality in immunosuppressed patients. Monoclonal antibody (mAb)-based therapeutic strategies are now being explored as a viable therapy option for severe sepsis and septic shock. Monoclonal antibodies may provide benefits through two major strategies: (a) monoclonal antibodies targeting the pathogen and its components, and (b) mAbs targeting inflammatory signaling may directly suppress the production of inflammatory mediators. The major focus of mAb therapies has been bacterial endotoxin (lipopolysaccharide), although other surface antigens are also being investigated for mAb therapy. Several promising candidates for mAbs are undergoing clinical trials at present. Despite several failures and the investigation of novel targets, mAb therapy provides a glimmer of hope for the treatment of severe bacterial sepsis and septic shock. In this review, mAb candidates, their efficacy against controlling infection, with special emphasis on potential roadblocks, and prospects are discussed.
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