Eosinophils in the pathogenesis of pancreatic disorders

Manohar, Murli; Kandikattu, Hemanth Kumar; Venkateshaiah, Sathisha Upparahalli; Yadavalli, Chandra Sekhar; Mishra, Anil

doi:10.1007/s00281-021-00853-0

Cited by 10 publications

(15 citation statements)

References 101 publications

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“…An enlarged sausage-like pancreas is described in AIP; whereas, an enlarged pancreatic head or tail is characteristic of EP. 13 Our initial case was significant for eosinophilia as well as histology significant for AIP; thus, imaging was used to support the diagnosis of Type 2 AIP.…”

Section: Discussionmentioning

confidence: 97%

“…Although lymphocytes are commonly seen in AIP, both AIP and EP are known to have eosinophils. 13 Furthermore, an analysis completed by Sah et al showed that in histologically proven type 2 AIP 21% of patients had peripheral eosinophilia and of these patients 50% had moderate to severe infiltration in the pancreas. 14 Thus, it is important to consider other diagnostic criteria such as imaging, which fortunately is helpful in differentiating AIP and EP.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pediatric Autoimmune Pancreatitis

Becker,

Kumar,

Altaf

et al. 2023

Pancreas

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Objectives Autoimmune pancreatitis (AIP) is a rare form of a chronic, immune-mediated, inflammatory pancreatic condition. There is limited data regarding presentation and outcome in the pediatric population. We described a single-center case series of 4 pediatric patients with AIP to better understand the presentation, symptoms, and outcomes of this rare condition. Methods Data collected included demographics, serology markers, symptoms at presentation, imaging, additional organ involvement, histology, treatment methods, and outcomes. The diagnosis of AIP was made by a combination of serology, pancreatic imaging, histology, extrapancreatic manifestations, and steroid response. Results All patients were diagnosed with type 2 AIP. Abdominal pain, emesis, and obstructive jaundice were the most common symptoms at presentation. Autoimmune markers were negative. Cross-sectional abdominal imaging showed diffuse/focal pancreatic gland enlargement and common bile duct stricture universally and main pancreatic duct irregularity in half of the patients. Biopsies showed lymphoplasmacytic infiltration with associated pancreatic fibrosis and atrophy. Treatment with an 8-week tapering course of prednisone showed prompt response with resolution of symptoms and normalization of laboratory test results. Conclusions Our case series shows that AIP in children is a rare entity with a distinct clinical presentation, classical radiographic and histological features with good long-term prognosis.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Pediatric Autoimmune Pancreatitis

Becker,

Kumar,

Altaf

et al. 2023

Pancreas

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“…In the case of pancreatic disease, chronic pancreatitis (CP) is an inflammatory disorder caused by alcohol consumption, blockage of the pancreatic duct, and trypsinogen mutation [174]. In the initiation and progression of this disease, granulocyte infiltration is essential to pancreatic inflammation [175].…”

Section: Eosinophilic Gastrointestinal Diseases (Egid) and Pancreatic Disordersmentioning

confidence: 99%

Emerging Evidence for Pleiotropism of Eosinophils

Rodrigo‐Muñoz

Gil-Martínez

Sastre

et al. 2021

IJMS

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Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and allergic/asthmatic immune responses, as scientific studies arise, the paradigm about these cells is continuously changing, adding layers of complexity to their roles in homeostasis and disease. Developing principally in the bone marrow by the action of IL-5 and granulocyte macrophage colony-stimulating factor GM-CSF, eosinophils migrate from the blood to very different organs, performing multiple functions in tissue homeostasis as in the gastrointestinal tract, thymus, uterus, mammary glands, liver, and skeletal muscle. In organs such as the lungs and gastrointestinal tract, eosinophils are able to act as immune regulatory cells and also to perform direct actions against parasites, and bacteria, where novel mechanisms of immune defense as extracellular DNA traps are key factors. Besides, eosinophils, are of importance in an effective response against viral pathogens by their nuclease enzymatic activity and have been lately described as involved in severe acute respiratory syndrome coronavirus SARS-CoV-2 immunity. The pleiotropic role of eosinophils is sustained because eosinophils can be also detrimental to human physiology, for example, in diseases like allergies, asthma, and eosinophilic esophagitis, where exosomes can be significant pathophysiologic units. These eosinophilic pathologies, require specific treatments by eosinophils control, such as new monoclonal antibodies like mepolizumab, reslizumab, and benralizumab. In this review, we describe the roles of eosinophils as effectors and regulatory cells and their involvement in pathological disorders and treatment.

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“…Blood and tissue eosinophilia with marked degranulation have been reported in a number of allergic diseases associated with food ( Shukla et al, 2015 ; Kandikattu et al, 2019 ). EP is a relatively rare disease characterized by local or diffuse infiltration of eosinophils into the pancreas ( Tian et al, 2016 ; Manohar et al, 2021 ). EP is easily misdiagnosed as PC because of similarities in their clinical symptoms, and some cases of PC are associated with eosinophilia ( Euscher et al, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

Macrophages-induced IL-18–mediated eosinophilia promotes characteristics of pancreatic malignancy

et al. 2021

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Reports indicate that accumulated macrophages in the pancreas are responsible for promoting the pathogenesis of chronic pancreatitis (CP). Recently, macrophage-secreted cytokines have been implicated in promoting pancreatic acinar-to-ductal metaplasia (ADM). This study aims to establish the role of accumulated macrophage-activated NLRP3-IL-18-eosinophil mechanistic pathway in promoting several characteristics of pancreatic malignancy in CP. We report that in a murine model of pancreatic cancer (PC), accumulated macrophages are the source of NLRP3-regulated IL-18, which promotes eosinophilic inflammation-mediated accumulation to periductal mucin and collagen, including the formation of ADM, pancreatic intraepithelial neoplasia (PanINs), and intraductal papillary mucinous neoplasm. Most importantly, we show improved malignant characteristics with reduced levels of oncogenes in an anti–IL-18 neutralized and IL-18 gene deficient murine model of CP. Last, human biopsies validated that NLRP3-IL-18–induced eosinophils accumulate near the ducts, showing PanINs formation in PC. Taken together, we present the evidence on the role of IL-18–induced eosinophilia in the development of PC phenotype like ADM, PanINs, and ductal cell differentiation in inflammation-induced CP.

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Eosinophils in the pathogenesis of pancreatic disorders

Cited by 10 publications

References 101 publications

Pediatric Autoimmune Pancreatitis

Pediatric Autoimmune Pancreatitis

Emerging Evidence for Pleiotropism of Eosinophils

Macrophages-induced IL-18–mediated eosinophilia promotes characteristics of pancreatic malignancy

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