Long chain polyunsaturated fatty acids and inflammation Long
chain polyunsaturated fatty acids and inflammation Philip Calder
Professor of Nutritional Immunology University of Southampton Slide
2 Adhesion Chemoattractants Vasoactive mediators Local injury
Systemic effects (incl. inflammation) BLOODSTREAM TISSUE Rolling
Diapedesis Inflammatory cytokines Activated leukocyte Inflammatory
cytokines Inflammatory eicosanoids Reactive species Calder et al.
(2009) Brit. J. Nutr. 101, S1-S45 Slide 3 Diseases or conditions
that involve inflammation Rheumatoid arthritis Crohns disease
Ulcerative colitis Cystic fibrosis PsoriasisLupus Type-1 diabetes
Childhood asthma Adult asthma Allergic diseases Atopic diseases
COPDAtherosclerosis Acute cardiovascular events Response to surgery
Trauma & sepsis Neurodegenerative diseases Some cancers Body
wasting Obesity . Slide 4 What have fatty acids got to do with
inflammation? Fatty acid nutrition could influence metabolite
and/or hormone concentrations that in turn influence inflammation
Fatty acid nutrition could influence other factors (e.g. oxidised
LDL; oxidative stress) that in turn influence inflammation Direct
pro- or anti-inflammatory effects via surface or intracellular
fatty acid receptors Effects mediated via changes in inflammatory
cell membrane phospholipids Slide 5 => Fatty acids
differentially affect inflammation/immunity via cell surface (TLR4,
GPR120) and intracellular (PPAR- ) receptors Slide 6 Altered fatty
acid supply Altered composition of inflammatory cell phospholipids
Membrane alterations: rafts; order; trafficking Lipid mediators
Signal transduction pathways leading to gene expression Altered
inflammatory cell phenotype Altered inflammatory response Slide 7
Fish oil-derived long chain -3 PUFAs exert anti-inflammatory
effects by inhibiting production of arachidonic acid-derived
eicosanoids Slide 8 EPA is also a substrate for eicosanoid
synthesis Arachidonic acid EPA 2-series PGs 4-series LTs 3-series
PGs 5-series LTs STRONG WEAK Slide 9 -3 fatty acid exposure
Receptors Membrane composition Fluidity Raft assembly Substrates
for eicosanoids, resolvins etc. Signals Cell responses Altered
(patho)physiology (less inflammatory phenotype) Slide 10 Summary
Inflammation underlies many common conditions and diseases Fatty
acids can influence inflammation acting through cell surface and
intracellular receptors/sensors that control inflammatory gene
expression Human inflammatory cells typically contain a relatively
high amount of arachidonic acid -> precursor of inflammatory
eicosanoids -3 PUFAs from fish oil are readily incorporated into
inflammatory cells Fatty acid composition of inflammatory cells
affects membrane fluidity, membrane raft formation, signal
transduction processes leading to gene expression, and the pattern
of lipid and peptide mediators produced Through these effects fatty
acids can affect inflammatory cell responses and inflammatory
processes Fish oil ( -3 PUFAs) exerts anti-inflammatory actions in
vivo that may be associated with improved patient outcome Slide 11
Conclusions Fatty acid composition of inflammatory cells influences
their function Arachidonic acid, EPA and DHA contents seem to be
important Mechanisms by which fatty acids affect inflammation are
many and complex Long chain -3 PUFAs are anti-inflammatory There is
a theoretical basis, supported by much pre-clinical science, for
clinical benefit from increased long chain -3 PUFA supply in
various patient groups Dose (of -3 fatty acid) is important
