Is anyone familiar with meds that block IL-6 Trans-signalling?

[datadragon]

I'm interested in this hyperferritenemia theory, but I can't find any study linking IL-18/IFN-y to hyperferritinemia....(or to reduced hepcidin level).

@pattismith Here is where I initially got the information from which explains. Upon viral infection, IL-18 release induces a marked elevation of circulation ferritin, explaining the frequently observed hyperferritinemia in viral infections. IL-18 also stimulates Th1 immune responses, which play a crucial role in the host defense against intracellular microbes through the induction of IFN-γ. In contrast, bacterial infections are commonly associated with an extensive release of IL-1β, thereby stimulating the hepatocytic CRP secretion through the induction of IL-6. CRP, in turn, acts as innate weapon in early host defense by promoting the phagocytosis of bacteria. IL-1β also stimulates a Th17 immune response, which is crucial for epithelial and mucosal defense against extracellular bacteria. Thus, the IL-18 response in viral infections is responsible for hyperferritinemia, while bacterial infections are characterized by an IL-1β/IL-6 response, culminating in elevated plasma levels of CRP. https://pubmed.ncbi.nlm.nih.gov/27977798/

The activation of the NLRP3 inflammasome, results in the processing and secretion of active Interleukin 1 (IL-1b) and IL-18. An IL-1/IL-6 signature increases neutrophils and C-reactive protein (CRP), whereas an IL-18/IFN-y signature is characterized by hyperferritinemia (excess of an iron storage protein called ferretin in the blood) and cytopenia. https://www.pnas.org/doi/10.1073/pnas.2009017117

 

[pattismith]

@pattismith Here is where I initially got the information from which explains. Upon viral infection, IL-18 release induces a marked elevation of circulation ferritin, explaining the frequently observed hyperferritinemia in viral infections. IL-18 also stimulates Th1 immune responses, which play a crucial role in the host defense against intracellular microbes through the induction of IFN-γ. In contrast, bacterial infections are commonly associated with an extensive release of IL-1β, thereby stimulating the hepatocytic CRP secretion through the induction of IL-6. CRP, in turn, acts as innate weapon in early host defense by promoting the phagocytosis of bacteria. IL-1β also stimulates a Th17 immune response, which is crucial for epithelial and mucosal defense against extracellular bacteria. Thus, the IL-18 response in viral infections is responsible for hyperferritinemia, while bacterial infections are characterized by an IL-1β/IL-6 response, culminating in elevated plasma levels of CRP. https://pubmed.ncbi.nlm.nih.gov/27977798/

The activation of the NLRP3 inflammasome, results in the processing and secretion of active Interleukin 1 (IL-1b) and IL-18. An IL-1/IL-6 signature increases neutrophils and C-reactive protein (CRP), whereas an IL-18/IFN-y signature is characterized by hyperferritinemia (excess of an iron storage protein called ferretin in the blood) and cytopenia. https://www.pnas.org/doi/10.1073/pnas.2009017117

Thank you, I read the two papers, the second one quotes the first one so it doesn't bring anything new.

The first one says in the conclusion:

"It will also be important to assess the direct correlation between circulating concentrations of IL-18 and ferritin in viral infections, as current studies have only focused on either IL-18 or ferritin separately."

This means that in 2016, no link or correlation had been studied yet between IL18 and ferritin level.

 

[datadragon]

This means that in 2016, no link or correlation had been studied yet between IL18 and ferritin level.

Previous reports suggest that it is important to assess the direct association between circulating concentrations of IL-18 and ferritin in viral infections, as current studies have only focused on either IL-18 or ferritin separately. It has been proposed a model in which the inflammatory response to viral (IL-18/ferritin) and bacterial (IL-6/CRP) infections presents with specific plasma patterns of immune biomarkers. Accordingly, in this study, the increased IL-18 accompanied with increased values of ferritin suggests that IL-18/ferritin could be a biomarker for viral infection. In conclusion, this study report increased production of ferritin and IL-18 in children infected by various serotypes of dengue virus, in which both molecules were associated with the severity of disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863311/ (2019)

 

[pattismith]

Previous reports suggest that it is important to assess the direct association between circulating concentrations of IL-18 and ferritin in viral infections, as current studies have only focused on either IL-18 or ferritin separately. It has been proposed a model in which the inflammatory response to viral (IL-18/ferritin) and bacterial (IL-6/CRP) infections presents with specific plasma patterns of immune biomarkers. Accordingly, in this study, the increased IL-18 accompanied with increased values of ferritin suggests that IL-18/ferritin could be a biomarker for viral infection. In conclusion, this study report increased production of ferritin and IL-18 in children infected by various serotypes of dengue virus, in which both molecules were associated with the severity of disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863311/ (2019)

I found another one in EBV as well, so it seems rather common in acute viral infection:

Here, we show that IL-18 is markedly elevated during acute EBV infections and EBV-associated diseases, while ferritin concentrations are also elevated during acute EBV infection and correlate with IL-18.

https://academic.oup.com/jid/article/206/2/197/2192568?login=false