1. Long chain polyunsaturated fatty acids and inflammation
Philip Calder
Professor of Nutritional Immunology
University of Southampton

2. Calder et al. (2009) Brit. J. Nutr. 101, S1-S45
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

3. Diseases or conditions that
involve inflammation
Rheumatoid arthritis
Crohn’s disease
Ulcerative colitis
Cystic fibrosis
Psoriasis
Lupus
Type-1 diabetes
Childhood asthma
Adult asthma
Allergic diseases
Atopic diseases
COPD
Atherosclerosis
Acute cardiovascular events
Response to surgery
Trauma & sepsis
Neurodegenerative diseases Some cancers
Body wasting
Obesity …….

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

5. => Fatty acids differentially affect inflammation/immunity via cell surface (TLR4, GPR120) and intracellular (PPAR-g) receptors

6. of inflammatory cell phospholipids
Altered
fatty acid supply
Altered composition
of inflammatory cell phospholipids
Membrane
alterations: rafts; order; trafficking
Signal transduction
pathways leading to gene expression
Lipid mediators
Altered inflammatory cell phenotype
Altered inflammatory response

7. Fish oil-derived long chain w-3 PUFAs exert anti-inflammatory effects by inhibiting production of arachidonic acid-derived eicosanoids

8. EPA is also a substrate for
eicosanoid synthesis
Arachidonic acid EPA
2-series PGs series LTs 3-series PGs series LTs
“STRONG” “WEAK”

9. Altered (patho)physiology (less inflammatory phenotype)
w-3 fatty acid exposure
Receptors
Membrane composition
Fluidity
Raft assembly
Substrates for
eicosanoids,
resolvins etc.
Signals
Cell responses
Altered (patho)physiology
(less inflammatory phenotype)

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
w-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 (w-3 PUFAs) exerts anti-inflammatory actions in vivo that may be associated with improved patient outcome

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 w-3 PUFAs are anti-inflammatory
There is a theoretical basis, supported by much pre-clinical science, for clinical benefit from increased long chain w-3 PUFA supply in various patient groups
Dose (of w-3 fatty acid) is important