The immune imbalance in the second hit of pancreatitis is independent of IL-17A

Thomson, John-Edwin; Brand, Martin; Fonteh, Pascaline Nanga

doi:10.1016/j.pan.2018.01.007

Cited by 13 publications

(13 citation statements)

References 54 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study by our group demonstrated that a Th1/Th2 cytokine imbalance occurs during the second hit of AP, 35 which is supported by other studies which included surgical, trauma and burns patients. [36][37][38][39] This study demonstrates that at the mRNA level, IL-21 expression in plasma is increased in patients with SAP compared to MAP patients during the second hit of AP.…”

Section: Discussionsupporting

confidence: 81%

“…1 and 3) contrasts with a study suggesting that the Th17 response is not active during the second hit of AP. 35 The present study assessed IL-21 expression at both mRNA and plasma level and suggests that upregulation of IL21 is short-lived. The transient nature of this response suggests that sampling time may be crucial in deriving conclusions concerning Th17 responses during the second hit of AP.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis

Thomson

Nweke

Brand³

et al. 2019

Pancreas

Self Cite

View full text Add to dashboard Cite

Objectives: Interleukin (IL)-21 is a cytokine associated with tissue inflammation, autoimmune and infectious diseases. Organ dysfunction and death can occur in patients with acute pancreatitis in two distinct clinical phases. Initially, a systemic inflammatory response syndrome which may be followed by systemic sepsis from infected pancreatic necrosis, known as the 'second hit'. The expression and possible role of IL-21 in acute pancreatitis has not been established. Methods: Thirty-six patients with mild, moderate and severe acute pancreatitis were enrolled. Peripheral blood samples of patients were drawn on days 7, 9, 11, and 13. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine the expression and concentration of IL-21. Results: Interleukin-21 mRNA levels increased significantly at day 9 in severe (P = 0.002) pancreatitis compared to both the mild and control patient groups. At the protein level, IL-21 was elevated in severe acute pancreatitis patients compared to mild, although this was not significant. Furthermore, day 9 IL-21 was elevated in septic severe acute pancreatitis patients and patients with pancreatic necrosis. Conclusions: Interleukin-21 is transiently elevated in severe acute pancreatitis compared to the mild/moderate group and hence IL-21 may contribute to the immune imbalance that occurs in acute pancreatitis.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 90%

Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis

Thomson

Nweke

Brand³

et al. 2019

Pancreas

Self Cite

View full text Add to dashboard Cite

show abstract

“…The CBA Th1/Th2/Th17 assay was performed according to the manufacturer’s instructions (BD Biosciences, La Jolla, San Diego, CA, USA) and as previously described [ 46 ], but with minor modifications. In summary, unique antibody-coated beads were used to bind to cytokines present in the cell-free supernatant.…”

Section: Methodsmentioning

confidence: 99%

Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells

Fru

Nweke

Mthimkhulu

et al. 2021

Life

Self Cite

View full text Add to dashboard Cite

Drug delivery systems involving polymer therapeutics enhance drug potency by improved solubility and specificity and may assist in circumventing chemoresistance in pancreatic cancer (PC). We compared the effectiveness of the naturally occurring drug, betulinic acid (BA), alone and in a polymer conjugate construct of polyethylene glycol (PEG), (PEG–BA), on PC cells (MIA PaCa-2), a normal cell line (Vero) and on peripheral blood mononuclear cells (PBMCs). PEG–BA, was tested for its effect on cell death, immunomodulation and chemoresistance-linked signalling pathways. The conjugate was significantly more toxic to PC cells (p < 0.001, IC50 of 1.35 ± 0.11 µM) compared to BA (IC50 of 12.70 ± 0.34 µM), with a selectivity index (SI) of 7.28 compared to 1.4 in Vero cells. Cytotoxicity was confirmed by increased apoptotic cell death. PEG–BA inhibited the production of IL-6 by 4–5.5 fold compared to BA-treated cells. Furthermore, PEG–BA treatment of MIA PaCa-2 cells resulted in the dysregulation of crucial chemoresistance genes such as WNT3A, TXNRD1, SLC2A1 and GATA3. The dysregulation of chemoresistance-associated genes and the inhibition of cytokines such as IL-6 by the model polymer construct, PEG–BA, holds promise for further exploration in PC treatment.

show abstract

“…Consistent with current clinical evidence, animal models also confirmed that AP induces the expression of various proinflammatory cytokines, including IL-17, which reach a high level during the first week of AP ( 46 ). Although IL-17A is associated with the initiation of systemic inflammatory response syndrome in AP, IL-17A may not be the cause of sepsis in the second stage (pancreatic infection and necrosis) ( 47 ). Considering its high prognostic value and rapid availability, IL-17 is considered a promising reference marker among single indicators and enhances the predictive validity of AP.…”

Section: The Role Of Il-17 In Apmentioning

confidence: 99%

Role of Interleukin-17 in Acute Pancreatitis

Chen

Liu

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Acute pancreatitis (AP) is a leading cause of death and is commonly accompanied by systemic manifestations that are generally associated with a poor prognosis. Many cytokines contribute to pancreatic tissue damage and cause systemic injury. Interleukin-17 (IL-17) is a cytokine that may play a vital role in AP. Specifically, IL-17 has important effects on the immune response and causes interactions between different inflammatory mediators in the AP-related microenvironment. In this literature review, we will discuss the existing academic understanding of IL-17 and the impacts of IL-17 in different cells (especially in acinar cells and immune system cells) in AP pathogenesis. The clinical significance and potential mechanisms of IL-17 on AP deterioration are emphasized. The evidence suggests that inhibiting the IL-17 cytokine family could alleviate the pathogenic process of AP, and we highlight therapeutic strategies that directly or indirectly target IL-17 cytokines in acute pancreatitis.

show abstract

The immune imbalance in the second hit of pancreatitis is independent of IL-17A

Abstract: An immune imbalance exists in patients with SAP, however secreted IL-17A is not responsible for the second hit in AP.

Cited by 13 publications

References 54 publications

Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis

Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis

Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells

Role of Interleukin-17 in Acute Pancreatitis

Contact Info

Product

Resources

About