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Interferon Induces Persistent Viral Infection
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Interferon Induces Persistent Viral Infection

http://www.medicalnewstoday.com/releases/259039.php

studyforhope - can you describe this in more layman's terms?
14 Comments Post a Comment
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Avatar_m_tn
it is best to wait for studyforhope comments since i dont have this knowledge at all but a study on mice is obviously no meaning on humans and this is just a newsite with ignorants journalists reporting their way, not a research paper, so the title to me is just marketing more than a real fact on intf, the effect is probably real on mice and maybe on humans too but you can t say intf leads to persistant infection this is ridiculous you may well say this about antivirals on humans more than interferon.....
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Avatar_m_tn
Oldstone is one of the worlds top virologists/immunologist, so this is highest quality work and can be taken very seriously.

They work in the LCMV mouse model, which is the standard model for fundamental questions relating to immune responses to viral infections.

The key point of this research is that there are two kinds of interferons, which have different spectra of functioning.

The type i interferons, to which ifn alpha belongs, has, according to these results, a key function to reduce damage to the organism by activating negative regulators of immune aggressiveness, that is Il-10 and PD-1, which calm down T cell responses, limiting organ damage in a longer standing infection.

This is a control function that will allow you to survive and not loose an infected organ if the fight goes on too long and somehow could not have been won by the T cell attack that took place up to this point.

Thus this mechanism is a compromise to survive with a chronic infection instead of dying due to extended organ damage.

The type Ii interferons, to which interferon gamma belongs are the real fighter against viral infected cells, by its secretion from activated cd8 cells, also called CTLs, that will literally clear, without killing, the HBv cccDNA from an infected hepatocyte.
Ifn gamma is meant to act only locally and at very high concentrations and will rapidly deteriorate after its release, so as not to damage more distant sites in the body. It is highly effective, but has to be produced locally by the activated CTLs upon recognition of a class I epitope on the surface of an infected hepatocyte.

The overall message from this research is, that class I interferons have a strong immunomodulatory function in addition to more moderately activating locally interferon response genes in the infected cells.
This immunomodulatory function can have the negative consequence to tune down the effector side of the immune attack to early and cause the infection to become chronic. It is a compromise with the enemy, to avoid further damage due to intense fighting. Like the peace after gulf war one.

This might indeed be the reason, that even after a year of IFn alpha therapy we typically see only moderate response rates, while upon a CTL induced flare, clearance can be rapidly, within weeks, thanks to the interferon gamma that is produced.

The problem with IFN gamma is, that it cannot be given systemically, the concentrations that you will reach in the liver are not effective for the noncytolytic clearance effect, while the systemic side effects become unbearably intense.
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Avatar_m_tn

journalists always use exaggerated titles...

this immune suppression effect is obviously a danger in acute phase but what about chronic phase?i guess we are already suppressed in our chronic hbv birth infections and  little to lose
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Avatar_m_tn
The message from this research is that in a chronic infection, ifn alpha is actively  contributing to chronicity due to its partial suppressive effect on T cell immunity.

The potential  therapeutic consequence would be to block the IFN alpha receptor, which would reactivate the suppressed Tcell response and possibly lead to an elimination. The danger would be fulminant hepatitis.
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Avatar_m_tn
So could we say that the current IFN treatment for Hep B is not effective or is going to fail?

Regards,

Cyrus
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Avatar_m_tn
The current interferon treatment has moderate effectiveness and needs to be used wisely, adapted to the patients situation. Individual responses vary widely and cannot easily be predicted. IFN treatment in patients with a very low surface antigen level, that obviously signifies substantial already pre therapy existing mechanisms to reduce infected cell numbers can generate the final push to surface antigen seroconversion or at least  to a more permanent lower infected state.
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Avatar_m_tn
Dear studyforhope,

This study is really confusing the traditional thinking i.e. should I maintain moderate exercise to increase interferon production.  I am now on ETV + IFN combo (I just completed the 2nd dose IFN).  Many thanks.

Regards,

Cyrus
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Avatar_m_tn
Maintaining moderate exercise during ifn treatment is definitely a good idea, if you are able to do it. Dont think for a moment that it will reduce your chances to clear because you do that.  The study that was presented here is of a more fundamental nature.
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Avatar_m_tn
How about the moderate exercises for the one that are under no treatment ?

I think I remember that I read some time ago that moderate exercises will increase interferon gamma production.
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Avatar_m_tn
http://www.ncbi.nlm.nih.gov/pubmed/9272775 - this was one study that link the moderate and exhaust exercises to to inf production.

http://jap.physiology.org/content/59/2/426.abstract
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Avatar_m_tn
Can you help me to understand the relation betwen moderate exercises that will increase interferon gamma production and the study presented by Oldstone.
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Avatar_m_tn
Moderate exercise might increase T cell function. Oldstones paper points to the tune down mechanism exerted by alpha interferon upon prolonged acute stimulation to protect the organism from organ damage as a mechanism that could lead to chronic viral infections.
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Avatar_m_tn
"Moderate exercise might increase T cell function" - so moderate exercise is recomandet for all of us ?

Inf type I (alpha) will keep the damage under control, but moderate exercise will increase T cell function and will determine more Inf type II production (gamma), but as you mention this Inf type II have to be localy produced, so where this Inf type II will be produced during moderate exercise ?

or I get all wrong ?
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Avatar_m_tn
this type ii interferon will be produced locally by the tcells just as before, except that, due to the moderate exercise, by virtue of unknown mechanisms, their functionality and therefore capacity to produce it at proper signaling is now intensified.
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