Zinc 'keeps immune system in check'

[Vibrant62]

Note: This is a BBC report of a study that is due to be published, but does not yet appear to be fully available. This study may have relevance to management of the cytokine storm in H5N1/ pandemic influenza infection, when considered alongside this mouse model study http://www.ncbi.nlm.nih.gov/pubmed/17626596 Effect of oral gavage treatment with ZnAL42 and other metallo-ion formulations on influenza A H5N1 and H1N1 virus infections in mice. NB ZnAL42 is a study reference code for the zinc compound under examination, not a chemical formula i.e no aluminium is in the compound

http://www.bbc.co.uk/news/health-21372790
Zinc 'keeps immune system in check'

Researchers say they have gained a key insight into how zinc helps the immune system fight infection.

A study shows that zinc stops the immune system from spiralling out of control, as happens when people develop sepsis.

snip

After previous studies in mice, the researchers from Ohio State University had shown that zinc-deficiency could lead to excessive inflammation.

This is what happens in sepsis, when in response to a severe infection, the body goes into overdrive, with potentially fatal consequences.

Feedback loop

Through further experiments in human cells and animal studies the researchers found that a protein called NF-kB lured zinc into the immune cells that responded fastest to fight infection.

Once inside, the zinc then put the brakes on further activity in the NF-kB pathway, slowing down the immune response and limiting the amount of inflammation, the study, in Cell Reports, indicated.

It was effectively a feedback loop, stopping the process getting out of hand, the researchers said.

Study leader, Dr Daren Knoell, said: "The immune system has to work under very strict balance, and this is a classic example of where more is not always better.

"We want a robust inflammatory response, which is part of our natural programming to defend us against a bug.

"But if that is unchecked, and there is too much inflammation, then it not only attacks the pathogen but can also cause much more collateral damage."

snip

"The implications of the work extend beyond the impact of zinc on innate immune function," he said.

[Vibrant62]

The following study is also particularly interesting vis-a-vis NCoV and also Influenza. It remains to be seen if similar results are obtained in suitable in-vivo models.

Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture

http://www.plospathogens.org/article...l.ppat.1001176

[Vibrant62]

Full study of NF-KB/ Zinc Regulation of innate immune responses published here (see post #1. Although this study looks specifically at sepsis, potentially of relevance to H5N1 / ARDS cytokine dysregulation and/or secondary pneumonias as sequelae to influenza.)

http://www.cell.com/cell-reports/ful...2813%2900016-8

ZIP8 Regulates Host Defense through Zinc-Mediated Inhibition of NF-κB

Summary

Activation of the transcription factor NF-κB is essential for innate immune function and requires strict regulation. The micronutrient zinc modulates proper host defense, and zinc deficiency is associated with elevated inflammation and worse outcomes in response to bacterial infection and sepsis. Previous studies suggest that zinc may regulate NF-κB activity during innate immune activation, but a mechanistic basis to support this has been lacking. Herein, we report that the zinc transporter SLC39A8 (ZIP8) is a transcriptional target of NF-κB and functions to negatively regulate proinflammatory responses through zinc-mediated down-modulation of IκB kinase (IKK) activity in vitro. Accordingly, fetal fibroblasts obtained from Slc39a8 hypomorphic mice exhibited dysregulated zinc uptake and increased NF-κB activation. Consistent with this, mice provided zinc-deficient dietary intakes developed excessive inflammation to polymicrobial sepsis in conjunction with insufficient control of IKK. Our findings identify a negative feedback loop that directly regulates innate immune function through coordination of zinc metabolism.

[Emily]

http://link.springer.com/article/10....2604-5?LI=true

Neurochemical Research
March 2005, Volume 30, Issue 3, pp 311-314
Nitrite/Nitrate (NO x ) and Zinc Concentrations in Influenza-associated Encephalopathy in Children with Different Sequela

Hisashi Kawashima,
Masahiro Amaha,
Hiroaki Ioi,
Gaku Yamanaka,
Yasuyo Kashiwagi,
Masato Sasamoto,
Kouji Takekuma,
Akinori Hoshika,
Yasuo Watanabe

Abstract

NOx (NO2 and NO3) in CSF obtained from 22 patients with influenza-associated encephalopathy were higher than those of a control group. Within the different prognosis, there were no significant differences in NOx levels. By analyzing the serum obtained from patients infected with influenza, including encephalopathy, with others, the serum zinc levels did show marked differences between them. Four out of eleven patients with influenza-associated encephalopathy showed low zinc levels below the normal range. However, there were no significant differences in the zinc levels between the group with sequela and without sequela. These results indicate that the increase of NOx levels detected in influenza-associated encephalopathy relates to the low zinc levels, and both low molecules might play an important role for the cause of encephalopathy.