In vivo effect of anti-TNF agent (etanercept) in reactivation of latent toxoplasmosis

El-Sayed, Nagwa Mostafa; Ismail, Khadiga Ahmed; Badawy, Abeer Fathy; Elhasanein, K.F.

doi:10.1007/s12639-015-0712-y

Cited by 21 publications

(14 citation statements)

References 33 publications

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“…The finding that late-onset TXP is associated with etanercept is part of the problematic of steroid-refractory aGvHD requiring immunosuppressive regimen intensification. Tumour necrosis factor-a is essential for the control of T. gondii in the central nervous system during in vivo primary infection and etanercept treatment has been shown to facilitate experimental T. gondii reactivation [22,23].…”

Section: Discussionmentioning

confidence: 99%

A matched case–control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication

Ader

Bachy²,

Balsat

et al. 2016

Clinical Microbiology and Infection

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Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p <0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-α blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients.

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Section: Discussionmentioning

confidence: 99%

A matched case–control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication

Ader

Bachy²,

Balsat

et al. 2016

Clinical Microbiology and Infection

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“…Two other uninfected mice served as controls: PBS-treated group (PBS; n = 10); only etanercept-injected group (Etan; n = 10). Etanercept was intraperitoneally administered to mice of ME49+Etan group at a dose of 1 mg/kg/week for 4 weeks ( El-Sayed et al, 2016 ). Mice in the PBS group received PBS and mice in the Etan group received etanercept.…”

Section: Methodsmentioning

confidence: 99%

“…The host resists T. gondii infection by mediating Th1-type cellular immunity to generate pro-inflammatory cytokines. The role of TNF during parasites infection greatly depends on the strain of parasites, the state of infection, and the amount of induced TNF ( El-Sayed et al, 2016 ). The number of T. gondii in macrophages reduces through lysosomal fusion and parasitophorous vacuole (PV) disruption induced by TNF ( Andrade et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Risk Assessment of Etanercept in Mice Chronically Infected With Toxoplasma gondii

Yang

Wang

et al. 2018

Front. Microbiol.

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Toxoplasma gondii (T. gondii) is a zoonotic parasite that severely harms the health of the host. The cysts of T. gondii can reactivate from bradyzoites to tachyzoites, if the individual develops low or defective immunity, causing lethal toxoplasmosis. The host resists T. gondii infection by mediating Th1-type cellular immunity to generate pro-inflammatory cytokines. Tumor necrosis factor (TNF) is an important pro-inflammatory cytokine, which can induce lysosomal fusion of parasitophorous vacuole (PV) to kill parasites. Etanercept is a soluble TNF receptor fusion protein, which is widely used clinically to cure autoimmune diseases. The effects and specific molecular mechanisms of etanercept treatment on patients co-infected with autoimmune diseases and chronic toxoplasmosis are rarely reported. In our study, a mouse model of chronic infection with T. gondii and murine macrophages RAW264.7 cells infected with T. gondii were employed to investigate the impact of etanercept on the status of chronic infection. The cytokines levels and a series of phenotypic experiments in vivo and in vitro were measured. In the present study, the expression levels of TNF, IL-1β, and IL-6 were decreased and the brain cysts number was increased in mice chronically infected with T. gondii after being treated with etanercept. In vivo experiments confirmed that etanercept caused a decrease in the immune levels of the mice and activated the brain cysts, which would lead to conversion from chronic infection to acute infection, causing severe clinical and pathological symptoms. Murine macrophages RAW264.7 cells were pretreated with etanercept, and then infected with T. gondii. In vitro experiments, the expression levels of cytokines were decreased, indicating that etanercept could also reduce the cells’ immunity and promote the transformation of bradyzoites to tachyzoites, but did not affect the intracellular replication of tachyzoites. In summary, etanercept treatment could activate the conversion of bradyzoites to tachyzoites through reducing host immunity in vivo and in vitro. The results obtained from this study suggest that the use of etanercept in patients co-infected with autoimmune diseases and chronic toxoplasmosis may lead to the risk of activation of chronic infection, resulting in severe acute toxoplasmosis.

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“…It was suggested that treatment of the parasitic lesions with hydroalcoholic extract of T. vulgaris stimulates natural killer cells activity and releases nitric acid and tumor necrosis factor (TNF-α) from macrophages [26]. TNF-α plays a crucial role in controlling the infection caused by T. gondii because it can activate CD8+ T cytotoxic cells to transform into major cytotoxic effector cells for destroying tachyzoite-infected cells, restricting parasite dissemination throughout acute infection and inhibiting cyst formation throughout chronic infection [27,28].…”

Section: Tablementioning

confidence: 99%

In vivo effect of anti-TNF agent (etanercept) in reactivation of latent toxoplasmosis

Abstract: Toxoplasma gondii (T.

Cited by 21 publications

References 33 publications

A matched case–control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication

A matched case–control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication

Risk Assessment of Etanercept in Mice Chronically Infected With Toxoplasma gondii

Hepatoprotective activity of Thymus vulgaris extract against Toxoplasma gondii infection

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