Filgrastim + abx against Bb

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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.