Can worms defend our hearts? Chronic helminthic infections may attenuate the development of cardiovascular diseases

Magen, Eli; Borkow, Gadi; Bentwich, Zvi; Mishal, Joseph; Scharf, Shimon

doi:10.1016/j.mehy.2004.09.028

Cited by 35 publications

(25 citation statements)

References 32 publications

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“…New research work is finding that helminths secrete interesting molecules which may have beneficial effects for cardiovascular disease (170), bowel disease, arthritis (191), and even allergic diseases (246).…”

Section: Parasite Factorsmentioning

confidence: 99%

Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

2008

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SUMMARY Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.

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Section: Parasite Factorsmentioning

confidence: 99%

Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

2008

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“…The role of Th2 cells in atherosclerosis seems to be very complex and even contradictory. A potential protective role of Th2 response is discussed in few studies [117,118] , while Ait-Oufella et al [24] assume a potential proatherogenic function of Th2 cells within the complex interaction theater of CD4+ T cell subsets in atherosclerosis. Thus, the exact role of the Th2 response remains to be elucidated based on an improved understanding of the complex interplay between Th1, Th2, and other T cell populations such as Th17 and Tregs within the atherosclerotic scenario [18,24] .…”

Section: Potential Role Of Th2 Responses In Cvdmentioning

confidence: 99%

Antioxidants, inflammation and cardiovascular disease

Mangge¹

2014

WJC

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Multiple factors are involved in the etiology of cardiovascular disease (CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells, leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species (ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or, and even more likely, due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress, however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover, molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signaling pathways involved in the regulation of immunological, metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response, interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase (IDO) in monocyte-derived macrophages, fibroblasts, endothelial and epithelial cells. Neopterin, a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase (NOS) is induced in several cell types to generate nitric oxide (NO). NO, despite its low reactivity, is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin (BH4), which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic peroxynitrite (ONOO -) is formed solely in the presence of superoxide anion (O2 -). Neopterin and kynurenine to tryptophan ratio (Kyn/Trp), as an estimate of IDO enzyme activity, are robust markers of immune activation in vitro and in vivo . Both these diagnostic parameters are able to predict cardiovascular and overall mortality in patients at risk. Likewise, a significant association exists between increase of neopterin concentrations and Kyn/Trp ratio values and the lowering of plasma levels of vitamin-C, -E and -B. Vitamin-B deficiency is usually accompanied by increased plasma homoycsteine. Additional determination of NO metabolites, BH4 and plasma antioxidants in patients with CVD and related clinical settings can be helpful to improve the understanding of redox-regulation in health and disease and might provide a rationale for potential antioxidant therapies in CVD. REVIEWSubmit a

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“…Alternatively, defining how the parasite overcomes its host's immune response has shed light on anti-inflammatory and immunosuppressive mechanisms, and recently this has evolved to a point where data from animal models, and a lesser number of clinical observations, suggest that infection with helminth parasites may reduce the severity of multiple sclerosis (23), type I diabetes mellitus (49), asthma (47), inflammatory bowel disease (8,9,30,34), and perhaps cardiovascular disorders (24). However, although medical therapy based on infective organisms can, in some circumstances, be effective (42,43), this comes with the caveat that unpredicted side effects could offset any therapeutic benefits.…”

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confidence: 99%

Extracts of the Rat Tapeworm,Hymenolepis diminuta, Suppress Macrophage ActivationIn Vitroand Alleviate Chemically Induced Colitis in Mice

et al. 2010

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Analysis of parasite-host interactions can reveal the intricacies of immunity and identify ways to modulate immunopathological reactions. We assessed the ability of a phosphate-buffered saline-soluble extract of adult Hymenolepis diminuta to suppress macrophage (human THP-1 cell line, murine peritoneal macrophages) activity in vitro and the impact of treating mice with this extract on colitis induced by dinitrobenzene sulfonic acid (DNBS). A high-molecular-mass fraction of adult H. diminuta (HdHMW) or excretory/secretory products reduced macrophage activation: lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) and poly(I:C)-induced TNF-α and IL-6 were suppressed by HdHMW. The active component in the HdHMW extract was minimally sensitive to boiling and trypsin digestion, whereas the use of sodium metaperiodate, as a general deglycosylation strategy, indicated that the immunosuppressive effect of HdHMW was at least partially dependent on a glycan: treating the HdHMW with neuraminidase and α-mannosidase failed to inhibit its blockade of LPS-induced TNF-α production by THP-1 macrophages. Mice treated with DNBS developed colitis, as typified by wasting, shortening of the colon, macroscopic and microscopic tissue damage, and an inflammatory infiltrate. Mice cotreated with HdHMW (three intraperitoneal injections) displayed significantly less inflammatory disease, and this was accompanied by reduced TNF-α production and increased IL-10 and IL-4 production by mitogen-stimulated spleen cells. However, cotreatment of mice with neutralizing anti-IL-10 antibodies had only a minor impact on the anticolitic effect of the HdHMW. We speculate that purification of the immunosuppressive factor(s) from H. diminuta has the potential to lead to the development of novel immunomodulatory drugs to treat inflammatory disease.

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Can worms defend our hearts? Chronic helminthic infections may attenuate the development of cardiovascular diseases

Cited by 35 publications

References 32 publications

Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

Antioxidants, inflammation and cardiovascular disease

Extracts of the Rat Tapeworm,Hymenolepis diminuta, Suppress Macrophage ActivationIn Vitroand Alleviate Chemically Induced Colitis in Mice

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