The nature of human IL-6

Puel, Anne; Casanova, Jean‐Laurent

doi:10.1084/jem.20191002

Cited by 22 publications

(25 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, IL-6 (produced at comparable levels by the cells cultured in both supplements) is naturally connected with impaired inflammatory responses to localised tissue damage or with the impaired induction of acutephase proteins. In addition, it has previously been stated that "IL-6-producing cells" include bone marrow stromal cells, fibroblasts, and T cells [39], which supports our finding of the comparable levels of the formation of IL-6 by the MSCs cultured in both the iFBS-and PR-SRGF-supplemented media. The question is, therefore, whether the levels of particular pro-and anti-inflammatory molecules (defined by in vitro culturing) play a role or not (the level of IL-6 was one order of magnitude higher than the levels of IL-8, MCP-1, and RANTES) in the prediction of the balance of the immune response.…”

Section: Impact Of a Serum Alternative (Pr-srgf) On The Mscssupporting

confidence: 92%

The Impact of Various Culture Conditions on Human Mesenchymal Stromal Cells Metabolism

Tonarova

Lochovska

Pytlík

et al. 2021

Stem Cells International

View full text Add to dashboard Cite

In vitro and in vivo analyses are closely connected, and the reciprocal relationship between the two comprises a key assumption with concern to the conducting of meaningful research. The primary purpose of in vitro analysis is to provide a solid background for in vivo and clinical study purposes. The fields of cell therapy, tissue engineering, and regenerative medicine depend upon the high quality and appropriate degree of the expansion of mesenchymal stromal cells (MSCs) under low-risk and well-defined conditions. Hence, it is necessary to determine suitable alternatives to fetal bovine serum (FBS—the laboratory gold standard) that comply with all the relevant clinical requirements and that provide the appropriate quantity of high-quality cells while preserving the required properties. Human serum (autologous and allogeneic) and blood platelet lysates and releasates are currently considered to offer promising and relatively well-accessible MSC cultivation alternatives. Our study compared the effect of heat-inactivated FBS on MSC metabolism as compared to its native form (both are used as the standard in laboratory practice) and to potential alternatives with concern to clinical application—human serum (allogeneic and autologous) or platelet releasate (PR-SRGF). The influence of the origin of the serum (fetal versus adult) was also determined. The results revealed the key impact of the heat inactivation of FBS on MSCs and the effectiveness of human sera and platelet releasates with respect to MSC behaviour (metabolic activity, proliferation, morphology, and cytokine production).

show abstract

Section: Impact Of a Serum Alternative (Pr-srgf) On The Mscssupporting

confidence: 92%

The Impact of Various Culture Conditions on Human Mesenchymal Stromal Cells Metabolism

Tonarova

Lochovska

Pytlík

et al. 2021

Stem Cells International

View full text Add to dashboard Cite

show abstract

“…No deficiencies of IL-27RA or ciliary neurotrophic factor receptor have been described, but most of the immunological and extrahematopoietic phenotypes of patients with AR partial or complete GP130 deficiency have been seen in patients lacking IL-6R, IL-11R, LIF-R, or OSM-R deficiency (Schwerd et al, 2017;Shahin et al, 2019;Spencer et al, 2019;Nieminen et al, 2011;Mikelonis et al, 2014;Arita et al, 2008). Collectively, these findings suggest that many, perhaps even most, of the immunological abnormalities seen in patients with STAT3 deficiency, whether biological (high IgE levels), clinical (atopy and recurrent staphylococcal infections), or both (low levels of inflammation), are due to poor cellular responses to IL-6 (Puel and Casanova, 2019), whereas most of the skeletal abnormalities are due to poor responses to IL-11 (craniosynostosis and deciduous tooth retention) or LIF (scoliosis, osteoporosis). The apparent lack of CMC in patients with AR deficiency of IL-6R, IL-10RA, IL-10RB, IL-11R, IL-21R, IL-23R, IFNAR1, IFNAR2, LIF-R, or OSM-R deficiency (Schwerd et al, 2017;Spencer et al, 2019;Nieminen et al, 2011;Mikelonis et al, 2014;Arita et al, 2008;Martínez-Barricarte et al, 2018;Hernandez et al, 2019;Glocker et al, 2011;Kotlarz et al, 2014;Duncan et al, 2015) also suggested that the pathogenesis of impaired IL-17 immunity and CMC in patients with mutations in STAT3 or ZNF341 may involve the disruption of multiple cytokine responsive pathways (Minegishi et al, 2007;Puel et al, 2011;Béziat et al, 2018;Ma et al, 2016).…”

Section: Introductionmentioning

confidence: 95%

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome

Béziat¹,

Sj²,

Chen³

et al. 2020

Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients’ heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways.

show abstract

“…On the contrary, the absence of IL-6 activated signaling pathway leads to bacterial infections, such as, staphylococcal disease, and abnormal responses of the immune system including the presence of high levels of immunoglobulins E and eczema. 2 Moreover, IL-6 levels were shown to increase with age. 23 This corroborates with our finding that IL-6 values increased by 0.05 pg/ml per year of age in healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Defining IL‐6 levels in healthy individuals: A meta‐analysis

Said

Al-Reesi

Al-Shizawi

et al. 2020

Journal of Medical Virology

101

View full text Add to dashboard Cite

Background Interleukin‐6 (IL‐6) is produced by and impacts different cell types in human. IL‐6 is associated with different diseases and viral infections, including COVID‐19. To our knowledge, no normal values were reported for IL‐6 in the blood of healthy individuals. We have reviewed and performed a meta‐analysis on a total of 140 studies, including 12,421 values for IL‐6 in the blood of healthy adult donors. Among these studies, 83 did not report a mean value and the standard deviation. Therefore, for the statistical analysis, we used the values reported in 57 studies, which included 3166 values for IL‐6. Results The reported values for IL‐6 in the blood of healthy donors varied between 0 and 43.5 pg/ml. The pooled estimate of IL‐6 was 5.186 pg/ml (95% confidence interval [CI]: 4.631, 5.740). As the age increased by 1 year, IL‐6 values increased by 0.05 pg/ml (95% CI: 0.02, 0.09; p < .01). Though the heterogenicity, as determined by I2 statistics, was high in our study, the differences in IL‐6 values are still at the level of a few pg/ml, which might be related to the differences in the conditions that influence IL‐6 production in the healthy population. Conclusions This is the first meta‐analysis reporting the levels of IL‐6 in the blood of healthy donors based on a large number of studies and donors. Therefore the 95% CI values determined in our study could well serve as a reference range for quick decision‐making in clinical interventions, particularly those aiming to inhibit IL‐6, especially urgent interventions, for example, COVID‐19.

show abstract

The nature of human IL-6

Abstract: Countless functions have been attributed experimentally to IL-6. In this issue of JEM, Spencer et al. (https://doi.org/10.1084/jem.20190344) reveal essential, nonredundant functions of human IL-6. Patients with genetic deficiencies of the IL-6 receptor suffer from “hyper IgE syndrome.”

Cited by 22 publications

References 15 publications

The Impact of Various Culture Conditions on Human Mesenchymal Stromal Cells Metabolism

The Impact of Various Culture Conditions on Human Mesenchymal Stromal Cells Metabolism

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome

Defining IL‐6 levels in healthy individuals: A meta‐analysis

Contact Info

Product

Resources

About