Host interleukin 6 production regulates inflammation but not tryptophan metabolism in the brain during murine GVHD

Belle, Ludovic; Zhou, Vivian; Stuhr, Kara L.; Beatka, Margaret; Siebers, Emily M.; Knight, Jennifer M.; Lawlor, Michael W.; Weaver, Casey T.; Hashizume, Misato; Hillard, Cecilia J.; Drobyski, William R.

doi:10.1172/jci.insight.93726

Cited by 14 publications

(18 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-6 production together with indoleamine 2,3 deoxygenase upregulation played a central role in CNS GvHD by its action on host microglial cells. [ 34 ] In this model, IL-6 blockade could partially reversed neuroinflammation.…”

Section: Discussion and Literature Reviewmentioning

confidence: 93%

Case report

et al. 2017

View full text Add to dashboard Cite

Rationale:Central nervous system (CNS) involvement of graft versus host disease (GvHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic CNS GvHD symptoms are heterogeneous and include cerebrovascular manifestations, demyelinating disease and immune-mediated encephalitis. CNS-Acute GvHD is not formally defined in literature.Patients concerns and diagnoses:We report 7 cases of CNS-GvHD among which two had histological-proven disease. We reviewed 32 additional cases of CNS GvHD published in literature since 1990. In this cohort, 34 patients were transplanted for hematologic malignancies, and 5 for non-malignant hematopoiesis disorders. Of these patients, 25 had a history of chronic GvHD and immunosuppressive treatment had been decreased or discontinued in 14 patients before neurological symptoms onset. Median neurological disorder onset was 385 days [7-7320]. Patients had stroke-like episodes (n = 7), lacunar syndromes (n = 3), multiple sclerosis-like presentations (n = 7), acute demyelinating encephalomyelitis-like symptoms (n = 4), encephalitis (n = 14), mass syndrome (n = 1), and 3 had non-specific symptoms. Median neurological symptoms onset was 81.5 days [7-1095] for patients without chronic GVHD history versus 549 days [11-7300] for patients with chronic GVHD (P = 0.001). Patients with early involvement of CNS after allo-HSCT and no chronic GVHD symptoms were more frequently suffering from encephalitis (64% versus 28%, P = 0.07), whereas stroke-like episodes and lacunar symptoms were less frequent (9% versus 36%, P = 0.13).Interventions:34 patients with CNS-GvHD were treated with immunosuppressive therapy, including corticosteroids for 31 of them. Other treatments were intravenous immunoglobulin, plasmapheresis, cyclophosphamide, calcineurin inhibitors, mycophenolic acid, methotrexate and etoposide.Outcomes:27 patients achieved a response: 10 complete responses, 15 partial responses and 2 transient responses. Of 25 patients with sufficient follow-up, 7 were alive and 18 patients deceased after CNS-GvHD diagnosis.Lessons:CNS-related GvHD is a rare cause of CNS disorders after allo-HSCT and is associated with a poor prognosis.

show abstract

Section: Discussion and Literature Reviewmentioning

confidence: 93%

Case report

et al. 2017

View full text Add to dashboard Cite

show abstract

“…RNA-seq analysis of microglia cells in GvHD models found enhanced proinflammatory MAPK/NF-κB/TAK1 signal in microglia cells and activated various signal cascades in immune cells ( 46 ). MHC-unmatched bone marrow or splenocytes induced BALA/c mouse GvHD model revealed significant increased levels of IFN-γ, TNF-α, and IL-6 mRNA in the brain tissue ( 47 ). Therapeutic TAK1 inhibition can reduce microglial inflammation during CNS-GvHD ( 46 ).…”

Section: Introductionmentioning

confidence: 99%

“…The forced swimming test was used to evaluate animal behavior. It was observed that the struggle behavior of GVHD animals in the test increased significantly, which is a dysfunctional response ( 47 ). Mice given anti-IL-6R antibodies significantly reduced this effect ( 47 ).…”

Section: Introductionmentioning

confidence: 99%

A Case Report of Central Nervous System Graft-Versus-Host Disease and Literature Review

Zhang

Guan

et al. 2021

Front. Neurol.

View full text Add to dashboard Cite

As an adverse immune phenomenon, graft-versus-host disease often occurs after allogeneic hematopoietic stem cell transplantation. The incidence of acute and chronic graft-versus-host disease is about 40–60% and the mortality rate can reach 15%, which is a potentially fatal disease. There are rare GvHD cases involving the central nervous system. We reported a rare case of diffuse white matter changes after haploid bone marrow transplantation, summarizing its clinical manifestations and diagnosis and treatment in conjunction with the literature.

show abstract

“…Historically, it was considered that the CNS could not be affected by GVHD. However, over the last decade, preclinical data (Belle et al, 2017;Hartrampf et al, 2013;Sostak et al, 2004) and clinical case reports (Harvey et al, 2014;Openshaw et al, 1995;Sostak et al, 2010;Stefanou and Bischof, 2017;Voss and Bischof, 2010) progressively accumulated and CNS-GVHD is now becoming recognized as a true entity (Armstrong et al, 1997;Belle et al, 2017;Grauer et al, 2010;Hartrampf et al, 2013;Harvey et al, 2014;Maffini et al, 2017;Openshaw et al, 1995;Rouah et al, 1988;Ruggiu et al, 2017;Sostak et al, 2004;Sostak et al, 2010;Stefanou and Bischof, 2017;Voss and Bischof, 2010). Nevertheless, the diagnosis of CNS-GVHD still remains difficult mainly because of the low prevalence of the disease, confounding factors and heterogeneous clinical presentations.…”

Section: Discussionmentioning

confidence: 99%

Neuronal surface antibody-mediated encephalopathy as manifestation of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Pirotte

Forte

Lutteri

et al. 2018

Journal of Neuroimmunology

Self Cite

View full text Add to dashboard Cite

Although it remained controversial for a long time, central nervous system (CNS) involvement of graft-versus-host disease (GVHD) is now becoming recognized as a real nosological entity. Previous case reports have suggested heterogeneous clinical presentations and it is not excluded that the whole spectrum of manifestations has not yet been fully described. Here, we report the case of a 58-year-old man with chronic GVHD who developed a rapidly ingravescent encephalopathy. There was no evidence for CNS immune-mediated lesions on conventional imaging nor for cellular infiltration in the cerebrospinal fluid. Serum analyses revealed the presence of anti-neuronal antibodies directed against anti-contactin-associated protein 2 (anti-Caspr2), a protein associated with voltage-gated potassium neuronal channels. Functional imaging with 2-deoxy-2-[fluorine-18] fluoro- d-glucose integrated with computed tomography (18F-FDG PET-CT) demonstrated diffuse cortical and subcortical hypometabolism. The patient was treated with a combination of immunosuppressive agents (corticosteroids, cyclophosphamide and rituximab) and progressively recovered normal neurocognitive functions. Taken together, these data suggest that CNS-GVHD may manifest as a reversible antibody-mediated functional encephalopathy. This report suggests for the first time the interest of screening for anti-neuronal antibodies and functional imaging with brain 18F-FDG PET-CT in diagnosing this severe complication of allogeneic hematopoietic cell transplantation (alloHSCT).

show abstract

Host interleukin 6 production regulates inflammation but not tryptophan metabolism in the brain during murine GVHD

Cited by 14 publications

References 63 publications

Case report

Case report

A Case Report of Central Nervous System Graft-Versus-Host Disease and Literature Review

Neuronal surface antibody-mediated encephalopathy as manifestation of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Contact Info

Product

Resources

About