Lyme disease future or investigational therapies: Difference between revisions
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====New Developments==== | ====New Developments==== | ||
* | * It has been found that [[post treatment Lyme disease syndrome]] patients have higher amounts of ''[[Borrelia]]''-specific [[FoxP3|forkhead box P3]] (FoxP3) than healthy controls, indicating that [[regulatory T cell|regulatory T cells, by]] [[immunosuppression]], might play a role in the development of [[post treatment Lyme disease syndrome]]. | ||
* FoxP3 are a specific marker of regulatory [[T cells]].<ref>{{cite journal |author=Jarefors S, Janefjord CK, Forsberg P, Jenmalm MC, Ekerfelt C |title=Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals |journal=Clin. Exp. Immunol. |volume=147 |issue=1 |pages=18-27 |year=2007 |pmid=17177959 |doi=10.1111/j.1365-2249.2006.03245.x}}</ref> | * FoxP3 are a specific marker of regulatory [[T cells]].<ref>{{cite journal |author=Jarefors S, Janefjord CK, Forsberg P, Jenmalm MC, Ekerfelt C |title=Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals |journal=Clin. Exp. Immunol. |volume=147 |issue=1 |pages=18-27 |year=2007 |pmid=17177959 |doi=10.1111/j.1365-2249.2006.03245.x}}</ref> | ||
* The signaling pathway [[P38 mitogen-activated protein kinases]] (p38 MAP kinase) has | * The signaling pathway [[P38 mitogen-activated protein kinases]] (p38 MAP kinase) has been identified as promoting expression of pro-inflammatory [[cytokines]] from ''[[Borrelia]]''.<ref>{{cite journal |author=Ramesh G, Philipp MT |title=Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk1, Erk2, and p38 in the response of astrocytes to Borrelia burgdorferi lipoproteins |journal=Neurosci. Lett. |volume=384 |issue=1-2 |pages=112-6 |year=2005 |pmid=15893422 |doi=10.1016/j.neulet.2005.04.069}}</ref> | ||
* | * These new and ongoing immunological studies suggest that cell-mediated immune disruption in Lyme patients amplifies the inflammatory process, often rendering it [[chronic]] and self-perpetuating, regardless of whether the ''Borrelia'' bacterium is still present in the host, or in the absence of the inciting pathogen in an [[autoimmune]] pattern.<ref>{{cite journal |author=Singh SK, Girschick HJ |title=Toll-like receptors in Borrelia burgdorferi-induced inflammation |journal=Clin. Microbiol. Infect. |volume=12 |issue=8 |pages=705-17 |year=2006 |pmid=16842565 |doi=10.1111/j.1469-0691.2006.01440.x}}</ref> | ||
* Researchers hope that this new developing understanding of the [[biomolecular]] basis and [[pathology]] of cell-mediated signaling events caused by ''B. burgdorferi'' [[infection]] will lead to a greater understanding of immune response and [[inflammation]] caused by Lyme disease and, hopefully, new treatment strategies for [[chronic]], antibiotic-resistant disease. | * Researchers hope that this new developing understanding of the [[biomolecular]] basis and [[pathology]] of cell-mediated signaling events caused by ''B. burgdorferi'' [[infection]] will lead to a greater understanding of immune response and [[inflammation]] caused by Lyme disease and, hopefully, new treatment strategies for [[chronic]], antibiotic-resistant disease. | ||
==References== | ==References== | ||
Revision as of 18:14, 8 August 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Future and investigational therapies of Lyme disease are directed towards decreasing the pro inflammatory immune process and decreasing Th1 upregulation. Studies have also been conducted to test the role of neurohormones in neuropsychiatric complications of Lyme disease.
Future or Investigational Therapies
Neuroendocrine therapies
- A developing hypothesis is that the chronic secretion of stress hormones (specifically glucocorticoids and catecholamines) as a result of Borrelia infection may reduce the effect of neurotransmitters, or other receptors in the brain by cell-mediated pro-inflammatory pathways, thereby leading to the dysregulation of neurohormones.[1][2]
- This process is mediated via the hypothalamic-pituitary-adrenal axis.
- Additionally, tryptophan, a precursor to serotonin, appears to be reduced within the CNS in a number of patients with Lyme disease.[3]
- Antidepressants have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of IFN-gamma and IL-10, as well as TNF-alpha and IL-6 through a psycho-neuroimmunological process.[4]
- Antidepressants have also been shown to suppress Th1 upregulation.[5]
- These studies warrant investigation of antidepressants for use in a psycho-neuroimmunological approach for optimal pharmacotherapy of antibiotic refractory Lyme patients.
Hyperbaric oxygen therapy
- The use of hyperbaric oxygen therapy (which is used conventionally to treat a number of other conditions), as an adjunct to antibiotics for Lyme has been discussed.[6]
- Though there are no published data from clinical trials to support its use, preliminary results using a mouse model suggest its effectiveness against B. burgdorferi both in vitro and in vivo.[7]
Antifungal medications
- Anecdotal clinical research has shown potential for the antifungal azole medications such as fluconazole for the treatment of Lyme disease, but this has yet to be repeated in a controlled study or postulated a developed hypothetical model for its use.[8]
Alternative medicine
- One approach in the field of alternative medicine is the use of bee venom to treat Lyme disease because it contains the peptide melittin, which has been shown to exert inhibitory effects on Lyme bacteria in vitro; however, no clinical trials of this treatment have been carried out.[9]
New Developments
- It has been found that post treatment Lyme disease syndrome patients have higher amounts of Borrelia-specific forkhead box P3 (FoxP3) than healthy controls, indicating that regulatory T cells, by immunosuppression, might play a role in the development of post treatment Lyme disease syndrome.
- FoxP3 are a specific marker of regulatory T cells.[10]
- The signaling pathway P38 mitogen-activated protein kinases (p38 MAP kinase) has been identified as promoting expression of pro-inflammatory cytokines from Borrelia.[11]
- These new and ongoing immunological studies suggest that cell-mediated immune disruption in Lyme patients amplifies the inflammatory process, often rendering it chronic and self-perpetuating, regardless of whether the Borrelia bacterium is still present in the host, or in the absence of the inciting pathogen in an autoimmune pattern.[12]
- Researchers hope that this new developing understanding of the biomolecular basis and pathology of cell-mediated signaling events caused by B. burgdorferi infection will lead to a greater understanding of immune response and inflammation caused by Lyme disease and, hopefully, new treatment strategies for chronic, antibiotic-resistant disease.
References
- ↑ Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP (2005). "Cytokine dysregulation, inflammation and well-being". Neuroimmunomodulation. 12 (5): 255–69. doi:10.1159/000087104. PMID 16166805.
- ↑ Calcagni E, Elenkov I (2006). "Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases". Ann. N. Y. Acad. Sci. 1069: 62–76. doi:10.1196/annals.1351.006. PMID 16855135.
- ↑ Gasse T, Murr C, Meyersbach P; et al. (1994). "Neopterin production and tryptophan degradation in acute Lyme neuroborreliosis versus late Lyme encephalopathy". European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies. 32 (9): 685–9. PMID 7865624.
- ↑ Kubera M, Lin AH, Kenis G, Bosmans E, van Bockstaele D, Maes M (2001). "Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio". Journal of clinical psychopharmacology. 21 (2): 199–206. PMID 11270917.
- ↑ Diamond M, Kelly JP, Connor TJ (2006). "Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade". European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 16 (7): 481–90. doi:10.1016/j.euroneuro.2005.11.011. PMID 16388933.
- ↑ Taylor R, Simpson I (2005). "Review of treatment options for Lyme borreliosis". J Chemother. 17 Suppl 2: 3–16. PMID 16315580.
- ↑ Pavia C (2003). "Current and novel therapies for Lyme disease". Expert Opin Investig Drugs. 12 (6): 1003–16. PMID 12783604.
- ↑ Schardt FW (2004). "Clinical effects of fluconazole in patients with neuroborreliosis". Eur. J. Med. Res. 9 (7): 334–6. PMID 15337633.
- ↑ Lubke LL, Garon CF (1997). "The antimicrobial agent melittin exhibits powerful in vitro inhibitory effects on the Lyme disease spirochete". Clin. Infect. Dis. 25 Suppl 1: S48–51. PMID 9233664.
- ↑ Jarefors S, Janefjord CK, Forsberg P, Jenmalm MC, Ekerfelt C (2007). "Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals". Clin. Exp. Immunol. 147 (1): 18–27. doi:10.1111/j.1365-2249.2006.03245.x. PMID 17177959.
- ↑ Ramesh G, Philipp MT (2005). "Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk1, Erk2, and p38 in the response of astrocytes to Borrelia burgdorferi lipoproteins". Neurosci. Lett. 384 (1–2): 112–6. doi:10.1016/j.neulet.2005.04.069. PMID 15893422.
- ↑ Singh SK, Girschick HJ (2006). "Toll-like receptors in Borrelia burgdorferi-induced inflammation". Clin. Microbiol. Infect. 12 (8): 705–17. doi:10.1111/j.1469-0691.2006.01440.x. PMID 16842565.