Natural Mosquito repellents, West Nile Virus, Tumor Necrosis Factor and other related topics
Jacob Schor, ND
July 7, 2006
Canmore , Alberta
A relative heat wave up here in Canada over the last few weeks has resulted in the thickest clouds of mosquitoes anyone can remember. I've just returned from a drive up to Banff to pick up another case of Summer Survivor Mosquito Spray from John Kellas. We'll bring it home and have it at the office July 17 th when we get back to work.
I met John Kellas while ski touring up on the Wapta Ice Field in the spring of 2004. When John isn't working for Parks Canada he spends much of his time brewing up insect repellent. Working out doors much of the time inspired John to this hobby turned vocation. Each year his formula gets a bit more complex and brewing a batch becomes more of an art. Until talking to John I never thought of bug repellent as something that could be handmade or something one brewed. John talks about his products much like a cheese maker or brew master. You've heard of the Slow Food Movement, well John may be one of the few practitioners of ‘Slow Bug Spray Movement'. When he told me that the current batch was “especially good,” I jumped at the opportunity and doubled our order.
I confess to a fixation with mosquito repellents since West Nile Virus (WNV) arrived in Colorado a few years back. The Health Department already reported the first recorded cases of the 2006 season. Though it doesn't seem that we will have the wave of illness we had a few summers back, I'm still concerned. The more I read about this virus and see patients who have had it, the less I like it. In fact the more I want to never get it.
WNV can cause some rather nasty damage. Paralysis is the big one we worry about. [i] [ii] This often occurs during acute infection but may leave a long term polio-like syndrome of paralysis. [iii] Cases of vocal cord paralysis [iv] have been reported and to those sufferers I am particularly sympathetic.
Reports suggest that Tumor Necrosis Factor (TNF) has an anti-WNV action. [v] Which might be great to know but explaining the complex actions of TNF won't be simple. I think I may save that explanation for another newsletter.
Suffice to say that several drugs in common use suppress TNF and thus make a West Nile Virus infection worse. People taking these medications are at greater risk of injury or death from WNV infections. [vi] These drugs include: monoclonal antibodies, such as infliximab (Remicade®) or adalimumab (Humira®); or circulating receptor fusion proteins such as etanercept (Enbrel®). These drugs are used to treat various autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and psoriasis.
Several patients who have had WNV infections in the past have reported lingering symptoms that are reminiscent of the Chronic Fatigue Syndrome (CFS) caused by Epstein-Barr Virus (EBV). WNV inflames the microglial cells in the brain causing a chronic reaction that is similar to the changes caused by EBV in CFS. [vii] I think it will be only a matter of time until WNV serum antibodies will be routinely run in the initial work up for Chronic Fatigue.
A number of herbs are known to affect TNF production, most though focus on lowering levels. These should probably be avoided during acute infection with WNV. Berberine a chemical found in several different herbs does appear to increase TNF production. [viii] Though probably inappropriate during acute infections, some of the TNF lowering herbs may still be useful in the long run. The Chinese herb Scutellaria baicalensis is one example. Although it decreases TNF it also decreases microglial cell inflammation. [ix] Old herbal texts suggest an American Scutellaria species as being useful in treating the lingering effects, especially fatigue, following the flu. This makes me wonder whether this Chinese version of the herb may help in treating lingering WNV symptoms.
The bottom line is obvious. Better to not get West Nile Virus and the best way to do that is to avoid mosquito bites. Few of us wish to bath in chemical repellents more than absolutely necessary. Thus you should appreciate my interest in John Kellas and his homebrewed repellents.
John has a new product out this summer that we're also bringing home. It's designed specifically for use on, what these socially correct Canadians call “canine companions” or what we Americans still tactlessly call, dogs. Poppy is perfumed with some as I write this.
John has also added thick Emu oil repellent smear on lotion to his product line. We will bring some it back as well.
I wrote at length about Kellas' repellents in May of 2004. For more information about his products refer to that earlier letter at:
JAMA. 2003 Sep 10;290(10):1318.
Neurologic manifestations and outcome of West Nile virus infection.
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, and Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta , Ga 30333 , USA . firstname.lastname@example.org
CONTEXT: The neurologic manifestations, laboratory findings, and outcome of patients with West Nile virus (WNV) infection have not been prospectively characterized. OBJECTIVE: To describe prospectively the clinical and laboratory features and long-term outcome of patients with neurologic manifestations of WNV infection. DESIGN, SETTING, AND PARTICIPANTS: From August 1 to September 2, 2002 , a community-based, prospective case series was conducted in St Tammany Parish, La. Standardized clinical data were collected on patients with suspected WNV infection. Confirmed WNV-seropositive patients were reassessed at 8 months. MAIN OUTCOME MEASURES: Clinical, neurologic, and laboratory features at initial presentation, and long-term neurologic outcome. RESULTS: Sixteen (37%) of 39 suspected cases had antibodies against WNV; 5 had meningitis, 8 had encephalitis, and 3 had poliomyelitis-like acute flaccid paralysis. Movement disorders, including tremor (15 [94%]), myoclonus (5 [31%]), and parkinsonism (11 [69%]), were common among WNV-seropositive patients . One patient died. At 8-month follow-up, fatigue, headache, and myalgias were persistent symptoms; gait and movement disorders persisted in 6 patients. Patients with WNV meningitis or encephalitis had favorable outcomes, although patients with acute flaccid paralysis did not recover limb strength. CONCLUSIONS: Movement disorders, including tremor, myoclonus, and parkinsonism, may be present during acute illness with WNV infection . Some patients with WNV infection and meningitis or encephalitis ultimately may have good long-term outcome, although an irreversible poliomyelitis-like syndrome may result.
Department of Pathology, School of Biomedical Sciences and Institute for Biomedical Research, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
Murine embryo fibroblasts (MEF) transcribe tumor necrosis factor (TNF) mRNA and secrete soluble TNF in response to infection by West Nile virus (WNV) and TNF was demonstrated to be protective against WNV infection in vitro. TNF is not required for the WNV-induced upregulation of MHC-I expression on MEF, as TNF deficiency did not affect the upregulation of major histocompatibility complex class I (MHC-I) by WNV. Furthermore, NF-kappaB was activated by WNV in TNF-deficient MEF, demonstrating that WNV induces NF-kappaB activation in a TNF-independent manner. The subunits of NF-kappaB activated by TNF and WNV differed, WNV-activated a p65/p50 NF-kappaB complex while TNF-activated NF-kappaB was composed of p65, p50, and c-Rel. Furthermore, TNF-induced activation of NF-kappaB occurred earlier than WNV-induced NF-kappaB activation. The data demonstrate that WNV infection of MEF is associated with TNF production, but the WNV-induced activation of NF-kappaB and subsequent upregulation of MHC-I by WNV is TNF-independent.
nile virus meningoencephalitis and acute flaccid paralysis after infliximab
Differential responses of human brain cells to West Nile virus infection.
Neuroimmunology Laboratory, Minneapolis Medical Research Foundation, University of Minnesota Medical School , 55455, USA . email@example.com
In recent years, West Nile virus (WNV) has emerged as a major cause of encephalitis in the United States . However, the neuropathogenesis of this flavivirus is poorly understood. In the present study, the authors used primary human brain cell cultures to investigate two neuropathogenic features: viral replication and induction of cytokines. Although neurons and astrocytes were found to support productive WNV infection, viral growth was poorly permissive in microglial cells. Compared to neuronal cultures that sustained viral growth for at least 2 weeks, replication peaked in astrocytes by 72 h post infection. In response to viral infection, astrocytes produced chemokines (CXCL10 and CCL5), but none of the cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, interferon alpha or gamma) tested could be detected. Although microglial cells failed to support viral replication, WNV induced production of the proinflammatory cytokines IL-6 and TNF-alpha. Microglial cells also released robust amounts of the chemokines CXCL10 and CCL2, as well as lower levels of CCL5, in response to WNV infection. WNV-induced chemokine and cytokine production by microglia was coupled with activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathways. Inhibition of p38 MAPK decreased chemokine production in response to WNV. Taken together, these findings suggest that microglial cell responses may influence the neuropathogenesis of WNV infection.
PMID: 16338745 [PubMed - indexed for MEDLINE]
Effect of berberine on interleukin 8 and monocyte chemotactic protein 1 expression in a human retinal pigment epithelial cell line.
Department of Ophthalmology, Toyama Medical and Pharmaceutical University , Toyama , Japan . firstname.lastname@example.org
PURPOSE: The aims of this study were to examine the effects of berberine, an alkaloid isolated from some medicinal herbs, on interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) expression in a human retinal pigment epithelial cell line (ARPE-19) stimulated with interleukin 1beta (IL-1beta) or tumor necrosis factor alpha (TNF-alpha). METHODS: ARPE-19 cells were cultured to confluence. Berberine and IL-1beta or TNF-alpha were added to the medium. IL-8 mRNA and MCP-1 mRNA were measured by semiquantitative reverse-transcription polymerase chain reaction and real-time polymerase chain reaction. IL-8 and MCP-1 protein concentrations in the media were measured using enzyme-linked immunosorbent assay. RESULTS: Berberine dose-dependently inhibited IL-8 mRNA and MCP-1 mRNA expression of the cells and protein levels in the media stimulated with IL-1beta or TNF-alpha. CONCLUSION: These findings indicate that berberine dose-dependently inhibited the expression of IL-8 and MCP-1 induced by IL-1beta or TNF-alpha. Copyright (c) 2006 S. Karger AG, Basel .
PMID: 16391493 [PubMed - in process]
Department of Anatomy and Neurobiology, Research Institute of Natural Science, Gyeongsang National University College of Medicine, 92 Chilam-dong, Jinju, Kyungnam 660-751, Korea.
Wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of a medicinal herb Scutellaria baicalensis Georgi, has been previously shown to have anti-inflammatory activities in various cell types including macrophages. In this work, we have found that wogonin is a potent neuroprotector from natural source. Wogonin inhibited inflammatory activation of cultured brain microglia by diminishing lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, and nitric oxide (NO) production. Wogonin inhibited NO production by suppressing inducible NO synthase (iNOS) induction and NF-kappaB activation in microglia. Inhibition of inflammatory activation of microglia by wogonin led to the reduction in microglial cytotoxicity toward cocultured PC12 cells, supporting a neuroprotective role for wogonin in vitro. The neuroprotective effect of wogonin was further demonstrated in vivo using two experimental brain injury models; transient global ischemia by four-vessel occlusion and excitotoxic injury by systemic kainate injection. In both animal models, wogonin conferred neuroprotection by attenuating the death of hippocampal neurons, and the neuroprotective effect was associated with inhibition of the inflammatory activation of microglia. Hippocampal induction of inflammatory mediators such as iNOS and TNF-alpha was reduced by wogonin in the global ischemia model, and microglial activation was markedly down-regulated by wogonin in the kainate injection model as judged by microglia-specific isolectin B4 staining. Taken together, our results indicate that wogonin exerts its neuroprotective effect by inhibiting microglial activation, which is a critical component of pathogenic inflammatory responses in neurodegenerative diseases . The current study emphasizes the importance of medicinal herbs and their constituents as an invaluable source for the development of novel neuroprotective drugs.
PMID: 12897065 [PubMed