Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)
n-3 Polyunsaturated fatty acids and autoimmune-mediated glomerulonephritis
Introduction
Inflammation is the normal host response to infection or injury that mediates immune elimination of pathogens and tissue repair [1]. Inflammatory processes include increased production of cytokines, chemokines, nitric oxide and eicosanoids by the innate immune system in conjunction with altered leukocyte homing, all of which can greatly impact acquired immunity. Aberrant inflammatory responses not only evoke acute injury, as exemplified by endotoxic shock, but contribute significantly to chronic autoimmune diseases. The capacity of dietary n-3 polyunsaturated fatty acids (PUFAs) found in fish oil to suppress inflammation-associated processes has made them attractive candidates for both the prevention and amelioration of a variety of organ-specific and systemic diseases [2], [3]. This review specifically discusses pre-clinical and clinical studies of the efficacy of n-3 PUFAs in prevention and treatment of autoimmune-mediated kidney diseases.
Section snippets
n-3 PUFAs, inflammation and immune response
Since mammals require but cannot synthesize fatty acids with double bonds distal to the ninth carbon atom, long chain PUFAs are essential to their diet [4]. Linoleic acid (18:2n-6) is a major PUFA found in oils derived from plant seeds such as corn or safflower. Linoleic acid can be elongated and desaturated to yield arachidonic acid (20:4n-6; AA). The action of Δ15-desaturase in plants converts linoleic acid to α-linolenic acid (18:3n-3) which can be elongated to eicosapentaenoic acid
Chronic kidney disease and autoimmune-mediated glomerulonephrides
The kidney’s primary function is to remove excess metabolic waste products and water from the blood [26], [27]. Damage to the glomeruli, the basic filtration units of the kidney, impairs this critical function. Glomerular damage can result from a kidney-specific disease or be a reflection of a broader systemic disease. Partial loss of kidney function is referred to as renal failure whereas total and permanent loss of kidney function is termed end-stage renal disease (ESRD). Both glomerular
Disease characteristics
IgAN is an autoimmune disease which has as its diagnostic hallmark diffuse mesangial deposition of IgA in kidney glomerulus frequently accompanied by haematuria. It has been estimated that IgAN affects almost 1% of the population and yet the diagnosis is often missed [30]. IgAN is extremely common worldwide accounting for up to 50% of glomerulonephropathies in Japan, 20–35% in Europe and 5–10% in North America [31], [32]. It has been estimated that IgAN is the most common glomerulonephritis and
Disease manifestations
Systemic lupus erythmatosus (SLE) affects 1 in 2500 Americans with most cases occurring in women of childbearing age (1:750) and in individuals of African and Asian descent (1:250) [106]. SLE etiology is complex with both genetic and environmental factors thought to contribute to its development. Defects in apoptotic cell clearance and aberrant uptake by macrophages appear to contribute to autoimmunity due to presentation of nuclear antigens to T and B cells [107]. Mortality from SLE is
Conclusions
Taken together, animal studies have demonstrated the potential for n-3 PUFAs to suppress onset (e.g. aberrant Ig production and glomerular deposition) and progression (e.g. inflammation, glomerular injury and proteinuria) of disease in several animal models of autoimmune glomerulonephritis. However, major gaps still exist in our understanding of the precise molecular mechanisms by n-3 PUFAs act and identities of their cellular targets. While several human clinical trials similarly suggest that
Acknowledgements
This work was supported by the Public Health Service Grants DK058833 and ES03358. The authors would like to acknowledge the assistance of Laura Vines and Mary Rosner in preparation of this manuscript.
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