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Linking TNF-Alpha and IFN-Gamme to CFS

Thursday, January 17 2002 - Filed under: General


I stumbled upon a very recent study from December 2001 and it fits the
puzzle very well:

I've found the link between Tumor Necrosis Factor-alpha and
and nitric oxide.
Both TNF-alpha and IFN-gamma are cytokines, released by activated
macrophages. 1
Both TNF-alpha and IFN-gamma are elevated in patients with a B19 virus
infection. 2
Both TNF-alpha and IFN-gamma are elevated in patients with CFS. 2
Both TNF-alpha and IFN-gamma cause an increase of nitric oxide synthase
(iNOS). 1 + 3 + 4 + 5
An increase in nitric oxide will cause lowered adrenal output. 6

The elevated nitric oxide and lowered cortisol feeds the nitric oxide
vicious cycle, as described on my site:

The interesting part of the 2001 study 2 is that TNF-alpha and
IFN-gamma are markedly elevated in both acute B19 virus infection *AND*
in follow-up of B19 virus infection.
Even though the serum anti-B19 Vp1/2 IgM antibodies are reduced to
*ZERO* in the follow-ups. During acute B19 virus infection these
antibodies are present in 100% of the patients. Check the table on page
5 of this study 2.

Some part of the virus remains in the body and keeps activating
macrophages, which in turn keep releasing TNF and IFN.
The IFN and TNF are both chronically elevated an so also the nitric
oxide synthase --} nitric oxide --} lowered adrenal output !

}The present study documents the cytokine dysregulation
}that occurs in patients both at the time of acute B19 virus
}infection and after a mean follow-up period of 22 +/- 5 months.
}Prolonged}chronic fatigue occurred in 13 of 39 patients
}followed-up and, in these patients, there was a signircant
}association between fatigue at follow-up with IFN-gamma }7
}pg/ml and/or TNF-a }40 pg/ml.

What to do know ?
I will aks my physician if he can determine my TNF-alpha and IFN-gamma
I am also interested in seeing my sedimentation rate.. I will know that
in one/two weeks.
What to do next will be difficult: Nobody knows which part of the virus
remains active in the body and nobody knows how to get this parts of
the virus out of the body.
I propose that this virus doesn't have to be a B19 virus, but it can
also be a mycoplasma or another virus or bacteria.

Anyone in this newsgroup that suffers from CFS and knows how low/high
his/her sedimentation rate, TNF-alpha and IFN-gamma levels are ?
I'm very interested in some feedback..


The Netherlands

1 New Animal Models for Heart Failure (links TNF to nitric oxide)
}Tumor necrosis factor (TNF), released by activated macrophages in the
}immune system, is one cytokine under investigation by Dr. Katz. TNF is
}thought to act on nitric oxide metabolism. In septic shock, in response
}to an endotoxin, the body overproduces TNF, nitric oxide dilates blood
}vessels, and the person goes into shock. Recently, however, Dr. Katz has
}found that high levels of TNF might not be detrimental in heart failure
}and TNF may preserve endothelial vasodilation
helial vasodilation

2 Circulating cytokines in B19 virus infection (2001 Study)
Circulating tumour necrosis factor-a and interferon-c are
detectable during acute and convalescent parvovirus B19
infection and are associated with prolonged and chronic fatigue
}Patients with CFS have been shown to have elevated levels of both serum
}IFN-c (Rasmussen et al., 1994) and TNF- a (Patarca et al., 1994; Moss et
}al., 1999) as compared to control cases. IFN-c appears to be a key
}mediator in cytokine dysregulation in the post-Q-fever fatigue syndrome
}(Penttila et al., 1998). In addition, recombinant IFN-c administration
}has been shown to result in fatigue symptoms (Mani & Poo, 1996).
}Recently, new therapies which target TNF-a or its receptor have been
}shown to improve mood and ameliorate fatigue (Choy & Panayi, 2001)..

}At acute B19 virus infection, detection of serum/plasma IL-6 was
}associated with rheumatoid factor (P _0?038) and IFN-c (&7 pg/ml) was
}associated with fatigue in those patients of &15 years of age (P
}_0?022). At follow-up, fatigue was associated with IFN-c (&7 pg/ml)
}and/or TNF-a (&40 pg/ml) (P _0?0275). Prolonged upregulation of serum
}IFN-c and TNF-a appears to represent a consistent host response to
}symptomatic B19 virus infection.

3 Enhancement of NO Production by interferon-gamma
}In the cytosolic fraction of surrounding site of microinjection with the
}vehicle, NOS activities was already detected. In brief, NO2- content was
}approximately 2.5 nmol/mg protein. After injection with vehicle, the
}content of NO2- did not change. On the other hand, the intrahippocampal
}injection with 1 unit of IFN-g plus 1 ?g of LPS significantly enhanced
}the content of NO2- after 24 hr. The intrahippocampal injection with
}IFN-g plus LPS significantly enhanced of NO2- accumulation (*P{0.002,
}two-way ANOVA).

4 Interferon-gamma causes Nitric Oxide synthase

5 Ethanol Suppresses NO Production and Inducible NOS Gene Expression
in Cultured Rat Glial Cells
} Among several cytokines released by LPS, TNF-a was more effective than
} interleukin-1b (IL-b ) and interferon g in stimulating NO production

6 Effect of L-NAME, a specific nitric oxide synthase inhibitor, on
corticotropin-releasing hormone-elicited ACTH and corticosterone
}These results indicate that in conscious rats NO plays a marked
}inhibitory role in the CRH-induced ACTH secretion and inhibits more
}potently corticosterone secretion
* Note: Corticosterone the same as cortisol in man

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