Title: Membrane Composition and Inflammation

Key words: PUFA, polyunsaturated fatty acids, phospholipid, cell membranes, linolenic acid, prostaglandins, cytokines, eicosanoids, fish oil, anti-inflammatory

Date: Dec 1999

Category: 6. The Body

Type: Article

Author: Dr van Rhijn

Membrane Composition and Inflammation

Introduction

Lipid soluble polyunsaturated fatty acids (PUFA’s) are integral components of complex phospholipid bilayer cellular membranes, modulating fluidity1, signalling pathways, enzymes, messengers and receptors involved in immune responses. Both n-3 and n-6 series PUFA's have immunomodulatory potential in illnesses and the potential sites for interaction lie within cell membranes2.

Polyunsaturated Fatty Acids (PUFA's)

Dietary n-6 parent fatty acid, linoleic acid (LA, C18:2 w -6), passes through sequential steps of desaturation and elongation3 to produce g -linolenic acid (GLA, C18:3 w -6 ) 4, dihomogammalinolenic acid (DHGLA, C20:3 w -6) and arachidonic acid (AA, C20:4 w -6).

In contrast, the parent n-3 fatty acid, a -linolenic acid (ALA, C18:3 w -3) produces the longer chain eicosapentaenoic acid (EPA, C20:5 w -3) and docosahexaenoic acid (DHA, 22:6 w -3) 5. The major PUFA's incorporated into cell membranes are the 20 carbon AA and EPA (highest affinity6) which are metabolised into biologically active eicosanoids7 by cyclooxygenases to prostanoids [prostaglandins (PG's) and thromboxanes (TX's)], and by lipoxygenases into leucotrienes (LT's).

AA (n-6) is the major precursor for the 2-series TX's & PG's and the 4-series LT's, whereas EPA (n-3) produces the 3-series TX's & PG's and the 5-series LT's8. ALA and LA compete for metabolic enzymes and a proper balance is essential to optimise the n-3 and n-6 content of cell membranes9.

Inflammatory Modulators

PG's and LT's play key roles as inflammatory modulators by influencing the production of cytokines10, 11, ultimately controlled by dietary and membrane incorporated PUFA's.

The PG3 & LT5 series12, derived from n-3 PUFA's (EPA), are 100-fold less potent biologically than the LT4 series from n-6 PUFA's (AA) with which they compete for cellular binding sites and are associated with decreased inflammatory responses13.

PA competitively inhibits AA metabolism and displaces AA14 from cell membrane phospholipids, thus reducing the biosynthesis of pro-inflammatory eicosanoids15, 16.

Supplementation

N-3 PUFA (fish oils) exert a generalised anti-inflammatory17 influence, by reducing cytokine (TNF a 18, IL-1b 19, IL-1a 20, IL-221 and IL-622, 23) production24 by mononuclear cells. Fish oil-fed animals had less fever in response to IL-1 (guinea-pigs)25, murine macrophages showed decreased TNF26 and IL-6 production27, exhibited a lesser degree of anorexia in response to IL-1 (rats)28 or TNF29 compared to other oils. EPA and coconut oil (low in LA) fed to rats, resulted in high lateral fluidity (peritoneal macrophages & hepatocytes) and suppressed pro-inflammatory cytokine production (TNF30 & IL-131) and responsiveness of tissue to inflammatory agents.

Other fats (butter, olive & maize) had opposing effects32. EPA also altered the leukotriene ratio LTB4/LTB5 towards an anti-inflammatory one by increasing LTB5 levels (patients with major surgery)33. Fish oil also diminished lymphocyte proliferation34, T-cell-mediated cytotoxicity35, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, adhesion molecule expression36 and C-reactive protein (inflammatory marker).

Conclusion

Dietary intake of PUFA’s leads to changes in the fatty acid composition of cell membranes and the balance of AA: EPA is particularly important, as it influences the type and biological efficacy of eicosanoids controlling inflammatory responses37.

References

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