The role of mercury exposure on Th-17/IL-33 axis.
Research type
Research Study
Full title
An ex vivo investigation into the role of mercury chloride exposure on the cytokines release associated with Th-17 axis and cytokine IL-33 from human peripheral blood mononuclear cells (hPBMCs) of Systemic lupus erythematosus (SLE) patients.
IRAS ID
275660
Contact name
Philip Allsopp
Contact email
Sponsor organisation
Ulster University
Duration of Study in the UK
1 years, 2 months, 31 days
Research summary
Systemic lupus erythematosus (SLE), also known as Lupus, is an autoimmune disease, which occurs when the body’s immune system attacks its own healthy tissue and might result in organ damage and death. \nLupus can affect multiple organs and has no specific symptoms; however the most typical complications are a characteristic ‘butterfly’ skin rash (usually present on the cheeks and around the nose), joint pain and in more severe cases kidney damage.\nIt remains unclear, what exactly cause SLE, however many genetic and environmental factors has been implicated in the initiation and progression of the disease. One of such environmental factor is mercury (Hg). Humans are exposed to methylmercury (MeHg) from fish consumption. However, fish is an important dietary source of beneficial to health nutrients, such as n-3 long chain polyunsaturated fatty acids (LCPUFA). N-3 LCPUFA are known to have potent anti-inflammatory properties; and long-term human studies have indicated that n-3 LCPUFAs present in the fish may help to mitigate any negative impact of MeHg in relation to cognitive performance. There are limited human studies investigating the role of n-3 LCPUFA on autoimmunity, however study by Duffy et al. (2004) demonstrated a protective effect of n-3 LCPUFA supplementation in Lupus patients, with reduction in disease activity following 24 weeks of supplementation.\nThe study proposed aims to build on previous research undertaken by Crowe et al., 2015, 2018, which demonstrated that Hg exposure to immune cells from SLE patients increases the production of a range of pro-inflammatory cytokines and that co-exposure with n-3 LCPUFA can reduce this Hg-associated inflammatory response. \n\nThe inflammatory markers investigated in by Crowe et al., 2015 was focused on Th-1 and Th-2-associated cytokines, which are thought to contribute to SLE disease activity, however there is accumulating evidence to support a role for the Th-17/IL-33 immune response in autoimmune pathogenesis, including SLE. \nTherefore, this study will aim to isolate immune cells from the blood of SLE patients and subsequently challenge the cells with Hg to determine if exposure can impact on Th-17 associated cytokine release. Furthermore, this study will also determine if co-exposure of the isolated immune cells to n3-LCPUFA can mitigate Hg-induced Th-17 cytokine release. \n
REC name
North of Scotland Research Ethics Committee 1
REC reference
20/NS/0039
Date of REC Opinion
19 Mar 2020
REC opinion
Favourable Opinion