Fish oils and Th17 cells

[Guest guest]

Dear All;

I've been boring everyone for some time now about the anti-

inflammatory effects of fish oils. But their exact mechanism(s) of

action have remained a bit of a mystery. Now an article by

Serhan and coworkers, just published in Nature Immunology, has shown

that Resolvin E1 (a very potent anti-inflammatory agent derived from

eicosapentaenoic acid (EPA), which is a major constituent of fish

oils), functions to block the production of interleukin 23 (IL-23)

and interleukin 6 (IL-6) in lung inflammation (asthma). Because IL-23

in particular promotes the production of Th17 cells (a newly

discovered set of T helper cells that are pro-inflammatory), the down-

regulation of IL-23 (and IL-6) limits production of Th17 cells and

therefore promotes resolution of lung inflammation:

__________________________

Nature Immunology Published online: 22 June 2008 | doi:10.1038/ni.1627

Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4

to promote the resolution of allergic airway inflammation.

Oliver Haworth, a Cernadas, Rong Yang, N Serhan & Bruce

D Levy

Pulmonary and Critical Care Medicine Division, Department of Internal

Medicine, Boston, Massachusetts 02115, USA.

Center for Experimental Therapeutics and Reperfusion Injury,

Department of Anesthesiology, Perioperative and Pain Medicine,

Brigham and Women's Hospital and Harvard Medical School, Boston,

Massachusetts 02115, USA.

Correspondence to: Bruce D Levy1,2 e-mail: blevy@...

Abstract

Interleukin 23 (IL-23) is integral to the pathogenesis of chronic

inflammation. The resolution of acute inflammation is an active

process mediated by specific signals and mediators such as resolvin

E1 (RvE1). Here we provide evidence that RvE1, in nanogram

quantities, promoted the resolution of inflammatory airway responses

in part by directly suppressing the production of IL-23 and IL-6 in

the lung. Also contributing to the pro-resolution effects of RvE1

treatment were higher concentrations of interferon-gamma in the lungs

of RvE1-treated mice. Our findings indicate a pivotal function for IL-

23 and IL-6, which promote the survival and differentiation of IL-17-

producing T helper cells, in maintaining inflammation and also

identify an RvE1-initiated resolution program for allergic airway

responses.

____________________

In their paper they also note that " IL-23 is involved in the

pathobiology of many chronic diseases, including colitis,

encephalitis, psoriasis, rheumatoid arthritis and cancer, and is

critical for the survival of Th17 cells. " They have previously shown

that Resolvin E1 protects against colitis in animal models, but had

not nailed this protective effect down to inhibition of IL-23, IL-6

and Th17 cell production at the time. They now propose that " the

regulation of IL-23 and Th17 cells by RvE1 may serve as a common

mechanism for its pro-resolution actions in mucosal inflammation. "

All this fits with the recent genetic data indicating that IL-23R (a

receptor for IL-23 expressed on Th17 cells) is a major IBD and

psoriasis susceptibility gene, and begins to suggest some interesting

connections between asthma and IBD.

As I have said before in an article called:

Revenge of the Fish

http://www.pscpartners.org/NewsVol-1-6.pdf

Fish Oils are Converted to Resolvin E1

[if you are as dyslexic as me and Yoda, this spells " FORCE " !]

May the FORCE be with you.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)