Featured Articles
July 2009
Effects of Exercise Training on Inflammatory Markers in Patients with Heart Failure
Author: Josef Niebauer
Source: Heart Failure Review 2008;13:39–49
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Highlights:
- Over the past two decades, it has been recognized that chronic heart failure is no longer seen as merely a failure of the heart to provide adequate cardiac output, it is rather a multisystem syndrome, which not only affects the cardiovascular system but also effects on the humoral, neuroendocrine, renal, and musculoskeletal systems.
- It has become clear that many features of the syndrome of chronic heart failure can be explained by the known biological effects of inflammatory mediators including tumor necrosis factor-a, interleukin-6, and nitric oxide.
- Exercise training has been shown to be associated with decreased inflammatory cytokine activation both locally and systemically.
- Randomized trials document that chronic - as opposed to acute bouts of - exercise leads positive changes not only to the myocardium but also systemically, and is associated with a marked increase in maximal oxygen uptake, quality of life, reduced rate of hospitalization, and mortality.
Conclusion:
Despite the growing number of therapeutic options the number of patients with chronic heart failure continues to rise. Exercise training has been shown to reduce inflammation and benefit heart failure patients and can safely be considered a ‘‘poly-pill’’. Efforts have to be intensified in order to offer exercise training to as many of patients as possible.
June 2009
On the Use of Herbal Medicines in Management of Inflammatory Bowel Diseases: A Systematic Review of Animal and Human Studies
Authors: Roja Rahimi et al.
Source: Dig Dis Sci 2009;54:471–480
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Highlights:
Because of a lack of safety and efficacy of standard therapies, the use of herbal therapies for managing IBD is increasing, and such therapies have shown promising results. The article reviewed all reported herbal therapies established in animal models or used for managing human inflammatory bowel disease (IBD).
Herbal therapies show their effectiveness by several mechanisms:
- Regulate T cells and reduce proinflammatory cytokines such as IFN-g, TNF-a, IL-1b, and IL-12
- Reduce oxidative stress and increase antioxidants
- Inhibit leukotriene B4, a potent proinflammatory mediator playing a role in several inflammatory diseases such as rheumatoid arthritis, asthma, psoriasis, and IBD
- Inhibit NF-kappa B, transcription factors that promote the expression of more than 150 genes, many of which play important roles in the regulation of inflammation and cell death
- Reduce Cox-2 and iNOS levels
- Improve antiplatelet activity
Conclusion:
Herbal therapies have decreased the disease activity index, increased the rate of clinical response, shown clinical improvement and clinical remission, decreased the relapse rate, improved rectal bleeding and stool consistency, and reduced histological damage in patients with IBD.
May 2009
High Plasma Levels of MCP-1 and Eotaxin Provide Evidence for an Immunological Basis of Fibromyalgia.
Authors: Zhifang Zhang et al.
Source: Exp Biol Med 2008;233:1171–1180
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Highlights:
In this study, plasma levels of 25 cytokines and chemokines (inflammatory mediators) in 92 female patients with fibromyalgia (FM) and 69 family members were measured compared to 77 controls.
Findings:
- High levels of inflammatory mediators (MCP-1 and eotaxin) were found in patients and family members compared to controls.
- Plasma collected from patients increased the migration of immune and inflammatory cells.
- Muscle itself can secrete inflammatory mediators (MCP-1, eotaxin, and IP-10).
Conclusions:
- Inflammatory mediators may contribute to the symptoms of FM.
- Similar inflammatory profiles found in family members support the idea that FM has a genetic component.
April 2009
The biochemical origin of pain – Proposing a new law of pain: The origin of all pain is inflammation and the inflammatory response. Part 1 of 3 – A unifying law of pain
Author: Sota Omoigui
Source: Medical Hypotheses 2007;69:70–82
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Highlights:
- A unifying theory or law of pain is proposed, which states: The origin of all pain is inflammation and the inflammatory response. This law unifies all pain syndromes as sharing a common origin of inflammation and the inflammatory response. The theory suggests that physical and neuropathic pain, acute and chronic pain, peripheral and central pain including windup, neuroplasticity and central sensitization are a continuum of inflammation and the inflammatory response.
- Every pain syndrome has a unique inflammatory profile with a predominance of certain inflammatory mediators. This inflammatory profile is not static but dynamic and variable in the same patient and from one patient to another. The inflammatory profile is derived from the original injury or trauma and modified by ongoing injuries and aggravations including iatrogenic interventions.
It is important to understand that:
- Inflammation can exist without structural damage that is visible with our current imaging technology.
- Structural damage will result in inflammation and the inflammatory response.
- Inflammation and the inflammatory response will produce structural damage. Classification and treatment of pain syndromes should depend on the complex inflammatory profile and should not be based alone on symptomatology, structural pathology, genetic markers or presence of autoantibodies.
3. Principles for treatment of pain syndromes
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Determination of the inflammatory profile of the pain syndrome.
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Inhibition or suppression of production of the appropriate inflammatory mediators, e.g. with inflammatory mediator blockers or surgical intervention where appropriate.
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Inhibition or suppression of neuronal afferent and efferent (motor) transmission, e.g. with anti-seizure drugs or local anesthetic blocks.
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Modulation of neuronal transmission, e.g. with opioid medication.
March 2009
A Malignant Flame
Author: Gary Stix
Source: Scientific American 2008;18:48-51
Highlight:
Understanding chronic inflammation, which contributes to heart disease, Alzheimer’s and a variety of other ailments, may be a key to unlocking the mysteries of cancer.
- Until recently, cancer researchers had focused primarily on genetic changes as the underlying cause of the cancer.
- In this decade investigators have come to realize that the developing tumor can hijack the immune system’s inflammatory component-normally part of the wound-healing process-to foster tumor grow.
- Recent studies have shown chronic inflammation promotes tumor progression from a premalignant state to a full-blown cancer.
- Inflammation helps tumor build support system, a microenvironment, consisting of immune/inflammatory cells, chemical signals and blood vessels.
- With the support system, the tumor starts to invade surrounding tissues, the point at which it becomes fully malignant and metastatic.
- Anti-inflammatory treatment may join traditional chemotherapies, which in combination could keep solid tumors or premalignancies localized.
February 2009
Inflammation, genes and zinc in Alzheimer's disease
Authors: Sonya Vasto et al.
Source: Brain Research Reviews 2008;58:96-105
Abstract:
Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. AD has been linked to inflammation and metal biological pathway. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, Aβ, product of cleavage of a much larger protein, the β-amyloid precursor protein (APP) and neurofibrillary tangles. Amyloid deposition, due to the accumulation of Aβ peptide, is the main pathogenetic mechanism. Inflammation clearly occurs in pathologically vulnerable regions of AD and several inflammatory factors influencing AD development, i.e. environmental factors (pro-inflammatory phenotype) and/or genetic factors (pro-inflammatory genotype) have been described. At the biochemical level metals such as zinc are known to accelerate the aggregation of the amyloid peptide and play a role in the control of inflammatory responses. In particular, zinc availability may regulate mRNA cytokine expression, so influencing inflammatory network phenotypic expression.
Summary:
- The lateral damage caused by inflammation usually accumulates slowly, sometimes asymptomatically for years and can lead to severe tissue deterioration.
- Inflammation occurs in vulnerable regions of the AD brain, with increased pro-inflammatory cytokines which are hardly evident in normal brain.
- Chronically activated microglia cells in the brain can kill adjacent neurons by the release of highly toxic products such as reactive oxygen intermediates, nitric oxide, proteolytic enzymes, complement factors or excitatory amino acids.
- The microglia activation can be due to local or systemic inflammation. A strong local inflammatory stimulus such as a previous head trauma is a risk factor for AD.
- Anti-inflammatory non steroid drugs (NSAIDs) diminish the risk to develop AD.
- ApoE 4 mutation, a well-known genetic risk factor in late-onset AD, accelerates amyloid deposition and promotes Aβ aggregation and senile plaques (hall markers of AD).
- Subjects carrying ApoE 4 mutation nearly doubles the chance to develop AD whereas individuals not carrying ApoE 4 allele decreases the risk of AD by 40%.
- ApoE 4 mutation promotes inflammatory responses by an increased transactivation of NF-κB and an increased expression of the heme oxygenase-1.
- The influence of dietary fats on AD development was observed in subjects carrying ApoE 4 mutation only.
- The body does not store Zn and a constant dietary intake is essential.
- Bioavailability of zinc plays a key role in regulating inflammatory responses. Zinc inhibits NF-κB and subsequently limits TNF-α effects.
- In chronic inflammation, as it occurs in ageing and age-related diseases as AD, zinc is less available to fight stress and to support immune/inflammatory responses.
- Zinc deficiency adversely impacts production of Th1 cells, which can reduce the activity of NK and T cytotoxic cells, and lead to greater production of pro-inflammatory cytokines and oxidative stress.
January 2009
From inflammation to sickness and depression: when the immune system subjugates the brain
Authors: Dantzer R. et al.
Source: Nature Reviews Neuroscience, 2008;9:46-57.
Abstract:
In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.
Summary:
- Infections cause people to become sick and change their behaviour. They develop fever, sleep poorly, eat less, experience difficulty with memory and learning, withdraw socially and complain of pain and fatigue.
- Glial and macrophage-like cells in the brain respond to peripheral infection by synthesizing the same pro-inflammatory and anti-inflammatory cytokines as those produced by leukocytes. Several immune-to-brain communication pathways act in parallel; these include a fast neural afferent pathway and a slower humoral pathway that requires a relay in circumventricular organs and the brain vasculature.
The predominant pro-inflammatory cytokines that cause behavioural signs of sickness are interleukin-1b and tumour necrosis factor-a (TNF-a).
- Inflammation and sickness place a burden on working memory by reducing the ability of the short-term memory register to process environmental stimuli. This effect is likely to be responsible for the alterations in cognition that are caused by inflammation.
- Sickness is as normal to infection as the fear response is to a threatening predator. Its purpose is to promote survival of the organism.
- If infections do not resolve and peripheral inflammation continues unabated, clinical depression can develop over a background of sickness behavior.
- A mechanism for inflammation-associated depression is shunting of tryptophan away from serotonin synthesis, by activation of indoleamine 2,3 dioxygenase (IDO), an enzyme that is predominantly synthesized by myeloid cells, such as macrophages and microglia.
- IDO activity is stimulated mainly by TNF-a and interferon-g. This leads to the production of neuroactive tryptophan metabolites that can induce depression-like behaviour by altering glutamatergic neurotransmission.
- Ageing, obesity and other conditions associated with chronic inflammation increase the risk of development and persistence of inflammation-associated sickness and depression.
