Re: Filgrastim + abx against Bb

[Guest guest]

It my understanding form reading the German literature- that the

pathogen becomes " host-adapted " . I guess living within the same host

for 20 or 30 years- would give some of the variants an edge at

survival- regardless of what abx was used.

Barb

>

> http://www.lymenet.de/

>

> (Datum: 13.4.2006)

>

> Isabel Diterich, Immunomodulation and new therapeutic strategies

in

> Lyme borreliosis, Dissertation (Dr. rer. nat.), Universität

Konstanz,

> 2003.(im Cache)

>

> 7 Summary

> If infection with Borrelia burgdorferi is not treated

adequately

> with antibiotics in an early stage, it may lead to Lyme

borreliosis

> (LB), a chronic multisystemic disorder which is difficult to cure.

In

> some cases the pathogen survives in spite of antibiotic

treatments.

> It is challenging to understand why Borrelia are often not

> eradicated, although being recognized by the host's immune defense

> and occasionally inducing a strong inflammatory reaction. Thus, it

> remains an area of debate how this pathogen persists in human

tissues.

>

> This question was addressed in the present thesis, examining

> possible immune evasion mechanisms of Borrelia.

>

> * Blood cells from patients suffering from persistent LB

> released significantly lower levels of pro-inflammatory cytokines

> (TNF‡ and IFN‹) in response to either Borrelia lysate or to

> lipopolysaccharide (LPS) in comparison to cells from healthy

volunteers.

> * In blood from healthy volunteers Borrelia lysate led to

> strong production of anti-inflammatory IL-10 and G-CSF, while

> inducing only low levels of proinflammatory IFN‹, compared to LPS.

> * Similar to endotoxin tolerance, different Borrelia

> preparations desensitized human blood monocytes on re-stimulation

> with either stimulus.

> * Borrelia-specific stimuli induced cross-tolerance

towards

> heterelogous stimuli such as lipopolysaccharid (LPS) and

lipoteichoic

> acid (LTA) in human monocytes.

> * Toll-like receptor (TLR) 2 but not TLR4 was required

for

> Borrelia-induced tolerance and cross-tolerance, as shown in

> experiments with knock-out mice.

> * PBMC tolerized by Borrelia lysate exhibited reduced TLR2-

> mRNA levels. Further, IL-10 was identified as a key mediator

involved

> in tolerance-induction by Borrelia lysate.

> * Combination of Filgrastim treatment with Ceftriaxone in

a

> late stage LB-patient who failed standard antibiotic therapy led

to

> successful eradication of the pathogen and complete regression of

> symptoms.

> * The mouse model of Borrelia infection was set up and

> characterized in order to study the therapeutic effects of

Filgrastim

> in vivo.

> * Treating immunocompetent and immunodeficient SCID mice

> with Filgrastim, as an immunosupportive therapy of LB did not

> attenuate the characteristic ankle swelling induced by Borrelia

> infection.

> * Regular application of Filgrastim led to an enhanced

> elimination of Borrelia from various organs in SCID mice. In

> immunocompetent mice this effect was less pronounced.

>

> In summary, we propose that Borrelia modulate the host's

immune

> system in order to evade clearance in the immunologically

competent

> host. Tolerance could represent the mechanism inhibiting host

> response thereby enabling survival and persistence of the

pathogen.

> Promising results were obtained testing a novel treatment strategy

> for late stage LB, a combination of Filgrastim as an

immunosupportive

> therapy with antibiotics. The respective clinical trial based on

> these findings was recently started.

>