Antimurine retroviral effect of doxycycline

[Natasa]

Methods Find Exp Clin Pharmacol. 1998 Oct;20(:643-7.

    Antimurine retroviral effect of doxycycline.

        * Sturtz FG.    Hopital Boucicaut, Oncology Department, Paris, France. fsturtz@club-internet.fr

    The tetracycline family is composed of several molecules whose antibacterial properties are due to the fixation on the bacterial ribosomes. Among those, doxycycline is one of the most potent antibiotics for which additional features have been recently discovered. Doxycycline has been found to inhibit metalloproteinases, to decrease gelatinolytic and metastatic activities of cancer cells, to have a "chondroprotective" effect in inflammatory arthritides, and to have strong antimalarial properties. In this study, a murine retrovirus producing cell line (psi CRIP-pXT1) was incubated in variable concentrations of doxycycline. The retroviral titer of this cell line was measured by the ability to transfer resistance to G418 to NIH/3T3 cells. The retroviral titer was significantly decreased by 70% when the packaging cells had been incubated with 25 microM of doxycycline at 37 degrees C. The ID50 was around 8 micrograms/ml. Astonishingly, this effect was not observed at 32 degrees C. The mechanism of this effect is still to be determined. It may be useful to be aware of this effect for uncovering all of the possible antiviral qualities of doxycycline and its related molecules, such as glycylcyclines or anthracyclines.

    PMID: 9922979 [PubMed - indexed for MEDLINE]

[kit]

Thanks for posting this!  Its pretty interesting this was effective at human body temperature and not below.

[awol]

This is really really interesting Natasa, and very relevant to my case.

I think my ME/CFS was triggered by vaccines before a trip to Ghana in 2002. However something that has always puzzled me is the fact that I actually felt really really good when I was in Ghana, and then my illness started full forced, never recovered, after I stopped taking my anti-malarials.

Well, it turns out that my anti-malarial was doxycycline!!! So I theorize that while I was in Ghana maybe my XMRV infection was put on hold by the doxycycline, but then started again full force as soon as I stopped!

[Cold_Taste_Of_Tears]

This is interesting as ME patients have lowered body core temperature, below the normal range.

[Hoping]

My illness was sudden onset in summer of 1988.  Late in '88 I had a surgical procedure and had a very bad infection following that.  I was put on doxycycline for 4 or 5 months in '89.  It was during this period that I started to very slowly recover from the severe weakness and fatigue that I had been suffering from since the prior summer. 

[jace]

I want a Px for Doxy!  (I know, I know)   

[kolowesi]

Thanks, Natasa,

This is mind-blowing for me. I've been on and off doxy for the last 10 years. Now I know why I go downhill fast without it. So far, I am negative by viral culture for XMRV, will retest I hope.

I've been on doxy for mycoplasma pneumoniae, "probable lupus," and chronic sinusitis. If I have been off for a while, I have a Herxheimer reaction when I restart it, so I always thought it was fighting bacteria. But that doesn't meant it wasn't helping in other ways as well.

Though my temp is often in the 97.0 F range, it still works for me. Might work even better if I had a "normal" temperature.

[MEkoan]

doxycycline really helps me

[awol]

MEkoan,

Are you taking it specifically for ME?

[MEkoan]

yeah, awol.

[awol]

was it easy to get a prescription?

[MEkoan]

It took a long time to make the connection and a longer time to be able to find a doctor who understood that it worked.  I will take this info to anyone I will see in the future.

I wonder if being on doxy could reduce the viral load to undetectable levels. 

It's the single most useful medication I've ever taken for ME.

peace...

[Gerwyn]

This could well be why


[size=-1]Circulation. 2009;119:2209-2216.)
 © 2009 American Heart Association, Inc. [/size]
 

Vascular Medicine

  Clinical Trial of Doxycycline for Matrix Metalloproteinase-9 Inhibition in Patients With an Abdominal AneurysmDoxycycline Selectively Depletes Aortic Wall Neutrophils and Cytotoxic T Cells  Jan H.N. Lindeman, MD, PhD; Hazem Abdul-Hussien, MD; J. Hajo van Bockel, MD, PhD; Ron Wolterbeek, MD; Robert Kleemann, PhD  [size=-1] From the Departments of Vascular Surgery (J.H.N.L., H.A.-H., J.H.v.B., R.K.) and Medical Statistics (R.W.), Leiden University Medical Center, and TNO–Quality of Life, Department of Vascular and Metabolic Diseases (R.K.), Leiden, the Netherlands. [/size]
 [size=-1]Correspondence to Jan H.N. Lindeman, MD, PhD, Department of Vascular Surgery, K6R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands. E-mail Lindeman@LUMC.nl[/size]
 Received July 16, 2008; accepted February 23, 2009.

[jace]

This is the extract G refers to:

Background—Doxycycline has been shown to effectively inhibit aneurysm formation in animal models of abdominal aortic aneurysm. Although this effect is ascribed to matrix metalloproteinase-9 inhibition, such an effect is unclear in human studies.

We reevaluated the effect of doxycycline on aortic wall protease content in a clinical trial and found that doxycycline selectively reduces neutrophil-derived proteases. We thus hypothesized that doxycycline acts through an effect on vascular inflammation.

Methods and Results—Sixty patients scheduled for elective open aneurysmal repair were randomly assigned to 2 weeks of low-, medium-, or high-dose doxycycline (50, 100, or 300 mg/d, respectively) or no medication (control group). Aortic wall samples were collected at the time of operation, and the effect of doxycycline treatment on vascular inflammation was evaluated.

Independently of its dose, doxycycline treatment resulted in a profound but selective suppression of aortic wall inflammation as reflected by a selective 72% reduction of the aortic wall neutrophils and a 95% reduction of the aortic wall cytotoxic T-cell content (median values; P<0.00003).

 Evaluation of major inflammatory pathways suggested that doxycycline treatment specifically quenched AP-1 and C/EBP proinflammatory transcription pathways (P<0.0158, NS) and reduced vascular interleukin-6 (P<0.00115), interleukin-8 (P<0.00246, NS), interleukin-13 (P<0.0184, NS), and granulocyte colony-stimulating factor (P<0.031, NS) protein levels. Doxycycline was well tolerated; there were no adverse effects.

Conclusions—A brief period of doxycycline treatment has a profound but selective effect on vascular inflammation and reduces aortic wall neutrophil and cytotoxic T-cell content. Results of this study are relevant for pharmaceutical stabilization of the abdominal aneurysm and possibly for other inflammatory conditions that involve neutrophils and/or cytotoxic T cells.

[Natasa]

hmmmmmmm

"...Another attempt at regulating CREB expression in brain is the tetracycline transactivator system, whereby doxycycline in the drinking water is the “switch” that is coupled to the suppression of transgene expression. CREB overexpression can subsequently be targeted to the brain, with a tetracycline transactivator (tTA) controlled by a 1.8kb neuron-specific enolase (NSE) promoter. Sakai and colleagues [101] crossed mouse lines to generate NSE-tTA TetOP-CREBα bi-transgenic mice, creating a system controlled by NSE, whose expression generates tTA, binding to the TetOP promoter, generating CREBα overexpression. Addition of a tetracycline analogue, doxycycline, binds to a Tet binding pocket on the tTA, which undergoes a conformational change and binds to TetOP in such a way, inhibiting CREBα expression...."

interesting in itself:
The nuclear transcription factor CREB: involvement in addiction, deletion models and looking forward.
http://tinyurl.com/24jygfj