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This paper describes the current literature on the molecular pathophysiology of interleukin-6 (IL-6) in the genesis of macular edema and on the outcomes with IL-6 inhibitors in the treatment of non-infectious macular edema. The role of IL-6 in the development of macular edema has been well elucidated. IL-6 is produced by multiple cells of the innate immune system and leads to a higher likelihood of developing autoimmune inflammatory diseases, such as non-infectious uveitis, through a variety of mechanisms. These include increasing the helper T-cell population over the regulatory T-cell population and leading to the increased expression of inflammatory cytokines, such as tumor necrosis factor-alpha. In addition to being key in the generation of uveitis and subsequent macular edema through these inflammatory pathways, IL-6 also can lead to the development of macular edema through other pathways. IL-6 induces the production of vascular endothelial growth factor (VEGF) and facilitates vascular leakage by downregulating tight junction proteins in retinal endothelial cells. Clinically, the use of IL-6 inhibitors has been found to be efficacious primarily in the context of treatment-resistant non-infectious uveitis and secondary macular edema. IL-6 is a key cytokine in retinal inflammation and macular edema. It is thus not surprising that the use of IL-6 inhibitors in treatment-resistant macular edema in the setting of non-infectious uveitis has been well documented as an effective treatment option. The use of IL-6 inhibitors in macular edema secondary to non-uveitic processes has only begun to be explored. [ABSTRACT FROM AUTHOR]

Stem cell transplantation is historically understood as a powerful preclinical therapeutic following stroke models. Current clinical strategies including clot busting/retrieval are limited by their time windows (tissue plasminogen activator: 3–4 h) and inevitable reperfusion injuries. However, 24+ h post-stroke, stem cells reduce infarction size, improve neurobehavioral performance, and reduce inflammatory agents including interleukins. Typically, interleukin-6 (IL-6) is regarded as proinflammatory, and thus, preclinical studies often discuss it as beneficial for neurological recuperation when stem cells reduce IL-6′s expression. However, some studies have also demonstrated neurological benefit with upregulation of IL-6 or preconditioning of stem cells with IL-6. This review specifically focuses on stem cells and IL-6, and their occasionally disparate, occasionally synergistic roles in the setting of ischemic cerebrovascular insults. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) is an acknowledged inflammatory cytokine with a pleiotropic action, mediating innate and adaptive immunity and multiple physiological processes, including protective and regenerative ones. IL-8 is a pro-inflammatory CXC chemokine with a primary function in attracting and activating neutrophils, but also implicated in a variety of other cellular processes. These two ILs are abundantly expressed at the feto-maternal interface over the course of a pregnancy and have been shown to participate in numerous pregnancy-related events. In this review, we summarize the literature data regarding their role in healthy and pathological pregnancies. The general information related to IL-6 and IL-8 functions is followed by an overview of their overall expression in cycling endometrium and at the feto-maternal interface. Further, we provide an overview of their involvement in pregnancy establishment and parturition. Finally, the implication of IL-6 and IL-8 in pregnancy-associated pathological conditions, such as pregnancy loss, preeclampsia, gestational diabetes mellitus and infection/inflammation is discussed. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use. Interleukin-6 (IL-6) is a potential biomarker in the context of the established role of neuroinflammation in TBI recovery. Therefore, a systematic review of the literature was performed to assess and summarise the evidence for IL-6 secretion representing a useful biomarker for clinical outcomes. A multi-database literature search between January 1946 and July 2021 was performed. Studies were included if they reported adult TBI patients with IL-6 concentration in serum, cerebrospinal fluid (CSF) and/or brain parenchyma analysed with respect to functional outcome and/or mortality. A synthesis without meta-analysis is reported. Fifteen studies were included, reporting 699 patients. Most patients were male (71.7%), and the pooled mean age was 40.8 years; 78.1% sustained severe TBI. Eleven studies reported IL-6 levels in serum, six in CSF and one in the parenchyma. Five studies on serum demonstrated higher IL-6 concentrations were associated with poorer outcomes, and five showed no signification association. In CSF studies, one found higher IL-6 levels were associated with poorer outcomes, one found them to predict better outcomes and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Despite some inconsistency in findings, it appears that exaggerated IL-6 secretion predicts poor outcomes after TBI. Future efforts require standardisation of IL-6 measurement practices as well as assessment of the importance of IL-6 concentration dynamics with respect to clinical outcomes, ideally within large prospective studies. Prospero registration number: CRD42021271200 [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of chronic, low-grade systematic inflammation for which exercise training (EX) and caloric restriction (CR) are potential treatments. We therefore performed a systematic meta-analysis to compare the effect of EX vs. CR and EX + CR vs. CR on inflammation markers in overweight and obese individuals. PubMed, Scopus, Web of Science and the Cochrane were searched up to April 2020 for EX vs. CR or EX + CR vs. CR interventions studies on inflammatory makers i.e. CRP, IL-6 and TNF-α in overweight and obese individuals. Standardized mean differences and 95% confidence intervals were calculated. Thirty two articles (reporting 38 trials) involving 2108 participants were included in the meta-analysis. Based on studies that directly compared EX and CR, there were no evidence for an effect of EX on IL-6 (p = 0.20) and TNF-α (p = 0.58), when compared with a CR. However, when compared to EX, CR has a statistically greater benefit on CRP (p = 0.01). In those studies, directly comparing EX + CR and CR, EX + CR caused a larger decrease in TNF-α (p = 0.002) and IL-6 (p = 0.02) and tended to decrease CRP (p = 0.06) when compared with CR. These results suggest that a combination of EX and CR may be more effective than CR alone at reducing inflammatory cytokines and CRP in overweight and obese individuals. [ABSTRACT FROM AUTHOR]

PubMed, ScienceDirect, Cochrane, Embase, Scopus, China National Knowledge Infrastructure (CNKI), Chinese Weipu, and Wanfang databases were searched to evaluate the effects of probiotics supplements on gastric cancer‐related inflammatory factors. Parallel randomized controlled trials (RCTs) assessing the effects of prebiotics supplement on gastric cancer patients were included in the review. Compared with routine nutrition, meta‐analysis shows that probiotics supplements reduce gastric cancer‐related inflammation levels by mostly increasing the levels of cluster of differentiation 4+ and greatly reducing the levels of interleukin‐6. Probiotics supplements can control the inflammatory response in cancer patients and may be a potential approach for controlling inflammatory levels in the patients. However, a larger population is needed for further study because of a certain degree of heterogeneity in this review. Practical applications: The effects of probiotics (Bifidobacterium, Lactobacillus, and Streptococcus species) on the gastric cancer‐related inflammation were investigated.Probiotics can reduce gastric cancer‐related inflammation levels more effectively by increasing the levels of cluster of differentiation 4+ and greatly reducing the levels of interleukin‐6.The study provides some theoretical basis for controlling cancer‐related inflammation responses in the patients using probiotics. [ABSTRACT FROM AUTHOR]

Background This meta-analysis evaluates the correlation between the IL-6 -174 G > C polymorphism and susceptibility of childhood sepsis. Methods: We searched PubMed, ISI Web of Knowledge, Scopus, CNKI, SID, SciELO databases until December 30, 2019 to identify all eligible studies. Results: A total of 17 studies with 1,287 cases and 2,482 controls were identified. Pooled data revealed that there was no significant association between the IL-6 -174 G > C polymorphism and risk childhood sepsis in the overall population. When stratified analysis was carried out by age group of cases, no associations were found in neonates and pediatrics. However, in ethnicity-based subgroups, a significant association was found in Caucasians and Africans. Conclusions: There was no significant association of the IL-6 -174G > C polymorphism with susceptibility to sepsis in childhood overall, but there was an association with the Caucasian and African ethnic subgroups. [ABSTRACT FROM AUTHOR]

We conducted a comprehensive analysis to explore whether multiple interleukin (IL), IL-1β, IL-4, IL-6, IL-8 and IL-10, polymorphisms and IL proteins (IL-6, IL-10) relate to lung cancer (LC) susceptibility or clinical characteristics. We performed the standard meta-analysis procedures according to PRISMA. The odds ratio (OR) and mean difference (MD) were used for analysis. We investigated 11 variants from 43 articles, and found that IL-1β rs16944 (p = 0.04) and IL-10 rs1800872 (p = 0.003) decreased while IL-10 rs1800896 (p = 0.007) increased LC risks. We also found that IL-1β rs1143627 decreased NSCLC risks (p = 0.03). The heterozygotes and homozygotes contributed differently. In addition, another 15 articles were involved to explore the relationship between IL proteins and LC. We found that LC patients accounted for higher serum IL-6 of 16.60 pg/mL (p < 0.00001) and higher serum IL-10 of 3.47 pg/mL (p = 0.02) than that of controls. Furthermore, IIIA-Ⅳ LC patients tended to have higher proportion of positive IL-6 staining in lung tumor tissue in contrast with IA-IIB patients by TNM stage (p = 0.0002). Four variants from IL-1β and IL-10, and serum IL-6 and IL-10 levels are associated with LC risks. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a dysregulated hyperinflammatory response. Authors review evidence on IL-6 and IL-6 blockade in coronavirus disease 2019 (COVID-19) and discuss the pathophysiological and prognostic roles of this cytokine and the clinical impact of pharmacological blockade of IL-6. The material includes original articles and reviews published from March 2020 to March 2021 and searched on PubMed, medRxiv, and bioRxiv. IL-6 is one of the most prominent pro-inflammatory cytokines. Increased levels are recorded in COVID-19 patients, especially those with severe-to-critical disease. Evidence is accumulating on the relevance of IL-6 as a prognostic marker in COVID-19. Since IL-6 is a druggable target for several inflammatory diseases, pharmacological blockers of the IL-6 signaling pathway were repurposed to blunt the abnormal SARS-CoV-2-induced cytokine release. Data are limited to few randomized controlled trials that reported encouraging, though not conclusive, results, indicating the usefulness of IL-6 blockade early in the course of the disease in patients with hyperinflammation and no or limited organ damage. Further research is warranted to explore the role of IL-6 in different COVID-19 phenotypes and identify subgroups of patients who may mostly benefit from IL-6 pathway inhibition. [ABSTRACT FROM AUTHOR]

• Clinical picture generally manifests as "overlap syndrome" and leads to vicious circle. • Early identification of rising cytokine storm and multilevel course of treatment is imperative. • Adjunctive treatment improves the success in fight with consequences of CRS. • Recognition of epigenetic factors might lead to personalized approach. Cytokine storm is a form of uncontrolled systemic inflammatory reaction activated by a variety of factors and leading to a harmful homeostatic process, even to patient's death. Triggers that start the reaction are infection, systemic diseases and rarely anaphylaxis. Cytokine storm is frequently mentioned in connection to medical interventions such as transplantation or administration of drugs. Presented mini-review would like to show current possibilities how to fight or even stop such a life-threatening, immune-mediated process in order to save lives, not only in COVID-19 patients. Early identification of rising state and multilevel course of treatment is imperative. The most widely used molecule for systemic treatment remains tocilizumab. Except for anti IL-6 treatment, contemporary research opens the possibilities for combination of pharmaceutical, non-pharmaceutical and adjunctive treatment in a successful fight with consequences of cytokine storm. Further work is needed to discover the exact signaling pathways that lead to cytokine storm and to determine how these effector molecules and/or combination of processes can help to resolve this frequently fatal episode of inflammation. It is a huge need for all scientists and clinicians to establish a physiological rational for new therapeutic targets that might lead to more personalized medicine approaches. [ABSTRACT FROM AUTHOR]

Background: Many studies have described the influence of -176G > C polymorphism of the IL-6 gene on susceptibility to preeclampsia. However, the results have remained inconclusive and controversial. Therefore, we performed a meta-analysis to more precisely determine the association between the IL-6 -176G > C polymorphism and preeclampsia risk. Methods: Electronic databases including PubMed, Embase, Web of Science, and CNKI were searched up to August 15, 2019. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to calculate the association. Results: A total of 12 studies with 1,821 preeclampsia cases and 3,339 controls were selected. Overall, no significant association was found between IL-6 -176G > C polymorphism and preeclampsia risk. In the stratified analyses by ethnicity, there was a significant association in Asians, but not in Caucasians and mixed populations. Conclusions: The results of meta-analysis indicated that IL-6 -176G > C polymorphism was not significantly associated with risk of preeclampsia in overall population. [ABSTRACT FROM AUTHOR]