Unravelling the broader complexity of IL-6 involvement in health and disease

Jenkins, Robert H.; Hughes, Stuart T.O.; Figueras, Ana Cardus; Jones, Simon A.

doi:10.1016/j.cyto.2021.155684

Cited by 16 publications

(17 citation statements)

References 273 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increases in IL-6 and TNF-α levels in CSF and brain parenchyma are considered markers of central inflammation in depression in the context of a possible increased microglia activity and reduction of astrocyte and oligodendrocyte markers [ 38 , 39 ]. Along with evidence of monocytic, lymphocytic, and microglial activation this suggests an activated inflammatory response system in MDD [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression

Дружкова

Yakovlev

Rider

et al. 2022

IJMS

View full text Add to dashboard Cite

Background: The hypothalamic-pituitary-adrenal (HPA) axis, inflammatory processes and neurotrophic factor systems are involved in pathogenesis of both epilepsy and depressive disorders. The study aimed to explore these systems in patients with focal epilepsy (PWE, n = 76), epilepsy and comorbid depression (PWCED n = 48), and major depressive disorder (PWMDD, n = 62) compared with healthy controls (HC, n = 78). Methods: Parameters of the HPA axis, neurotrophic factors, and TNF-α were measured in blood serum along with the hemogram. Results: Serum cortisol level was augmented in PWE, PWCED, and PWMDD compared with HC and was higher in PWMDD than in PWE. Serum cortisol negatively correlated with Mini–Mental State Examination (MMSE) score in PWE, and positively with depression inventory–II (BDI-II) score in PWMDD. Only PWMDD demonstrated elevated plasma ACTH. Serum TNF-α, lymphocytes, and eosinophils were augmented in PWMDD; monocytes elevated in PWE and PWCED, while neutrophils were reduced in PWE and PWMDD. Serum BDNF was decreased in PWE and PWCED, CNTF was elevated in all groups of patients. In PWE, none of above indices depended on epilepsy etiology. Conclusions: The results confirm the involvement of HPA axis and inflammatory processes in pathogenesis of epilepsy and depression and provide new insights in mechanisms of epilepsy and depression comorbidity.

show abstract

Section: Discussionmentioning

confidence: 99%

Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression

Дружкова

Yakovlev

Rider

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Many efforts have been made to target IL6. Most of the drugs that have been studied are monoclonal antibodies (e.g., clazakizumab, olokizumab, sirukumab, siltuximab and ziltivekimab) [ 12 ]. The possibility of targeting IL6 with small molecules has been investigated recently [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction

Povinelli

Zazeri

Jones

et al. 2022

IJMS

View full text Add to dashboard Cite

Herein, we elucidate the biophysical aspects of the interaction of an important protein, Interleukin-6 (IL6), which is involved in cytokine storm syndrome, with a natural product with anti-inflammatory activity, piperine. Despite the role of piperine in the inhibition of the transcriptional protein NF-κB pathway responsible for activation of IL6 gene expression, there are no studies to the best of our knowledge regarding the characterisation of the molecular interaction of the IL6-piperine complex. In this context, the characterisation was performed with spectroscopic experiments aided by molecular modelling. Fluorescence spectroscopy alongside van’t Hoff analyses showed that the complexation event is a spontaneous process driven by non-specific interactions. Circular dichroism aided by molecular dynamics revealed that piperine caused local α-helix reduction. Molecular docking and molecular dynamics disclosed the microenvironment of interaction as non-polar amino acid residues. Although piperine has three available hydrogen bond acceptors, only one hydrogen-bond was formed during our simulation experiments, reinforcing the major role of non-specific interactions that we observed experimentally. Root mean square deviation (RMSD) and hydrodynamic radii revealed that the IL6-piperine complex was stable during 800 ns of simulation. Taken together, these results can support ongoing IL6 drug discovery efforts.

show abstract

“…However, IL‐6 antagonism changes the lipid composition to lower cholesterol‐associated proatherogenic factors, such as HDL‐associated serum amyloid‐A and secretory phospholipase‐A2 [21,22]. Similar studies also identify prominent roles for IL‐6 in pain perception, psychological well‐being, the regulation of haematopoiesis, and processes affecting tissue turnover, regeneration and repair [8,18,23–26]. How IL‐6 signalling intermediates converge to regulate these homeostatic processes while at the same time supporting host defence and the response to tissue damage is unclear.…”

mentioning

confidence: 99%

“…Similar phenotypic traits are also seen in patients with mutations in STAT1 and STAT3, the principle downstream transcription factors of IL‐6 signalling [ 9 , 16 , 17 ]. Other examples have arisen from documentation of the clinical efficacy of biological drugs and small molecule inhibitors that block the IL‐6 pathway [ 1 , 4 , 18 ]. These include monoclonal antibodies that target IL‐6 (e.g.…”

mentioning

confidence: 99%

“…Here, its immunomodulatory activities are weighted against its contribution to the maintenance of barrier integrity in epithelial tissues [ 1 , 4 ]. IL‐6 is also essential for the regulation of lipid, glucose and iron metabolism, and is integral to the control of mitochondrial bioactivity [ 1 , 2 , 4 , 18 ]. These activities impact processes affecting appetite, fatigue and energy expenditure.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Making sense of IL‐6 signalling cues in pathophysiology

et al. 2021

Self Cite

View full text Add to dashboard Cite

Unravelling the molecular mechanisms that account for functional pleiotropy is a major challenge for researchers in cytokine biology. Cytokine–receptor cross‐reactivity and shared signalling pathways are considered primary drivers of cytokine pleiotropy. However, reports epitomized by studies of Jak‐STAT cytokine signalling identify interesting biochemical and epigenetic determinants of transcription factor regulation that affect the delivery of signal‐dependent cytokine responses. Here, a regulatory interplay between STAT transcription factors and their convergence to specific genomic enhancers support the fine‐tuning of cytokine responses controlling host immunity, functional identity, and tissue homeostasis and repair. In this review, we provide an overview of the signalling networks that shape the way cells sense and interpret cytokine cues. With an emphasis on the biology of interleukin‐6, we highlight the importance of these mechanisms to both physiological processes and pathophysiological outcomes.

show abstract

Unravelling the broader complexity of IL-6 involvement in health and disease

Cited by 16 publications

References 273 publications

Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression

Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression

A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction

Making sense of IL‐6 signalling cues in pathophysiology

Contact Info

Product

Resources

About