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2017 ; 31
(4
): 1273-1288
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Treating inflammation and infection in the 21st century: new hints from decoding
resolution mediators and mechanisms
#MMPMID28087575
Serhan CN
FASEB J
2017[Apr]; 31
(4
): 1273-1288
PMID28087575
show ga
Practitioners of ancient societies from the time of Hippocrates and earlier
recognized and treated the signs of inflammation, heat, redness, swelling, and
pain with agents that block or inhibit proinflammatory chemical mediators. More
selective drugs are available today, but this therapeutic concept has not
changed. Because the acute inflammatory response is host protective to contain
foreign invaders, much of today's pharmacopeia can cause serious unwanted side
effects, such as immune suppression. Uncontrolled inflammation is now considered
pathophysiologic and is associated with many widely occurring diseases such as
cardiovascular disease, neurodegenerative diseases, diabetes, obesity, and
asthma, as well as classic inflammatory diseases (e.g., arthritis and periodontal
diseases). The inflammatory response, when self-limited, produces a superfamily
of chemical mediators that stimulate resolution of the response. Specialized
proresolving mediators (SPMs), identified in recent years, are endogenous
mediators that include the n-3-derived families resolvins, protectins, and
maresins, as well as arachidonic acid-derived (n-6) lipoxins, which promote
resolution of inflammation, clearance of microbes, reduction of pain, and
promotion of tissue regeneration via novel mechanisms. Aspirin and statins have a
positive impact on these resolution pathways, producing epimeric forms of
specific SPMs, whereas other drugs can disrupt timely resolution. In this
article, evidence from recent human and preclinical animal studies is reviewed,
indicating that SPMs are physiologic mediators and pharmacologic agonists that
stimulate resolution of inflammation and infection. The findings suggest that it
is time to challenge current treatment practices-namely, using inhibitors and
antagonists alone-and to develop immunoresolvents as agonists to test resolution
pharmacology and their role in catabasis for their therapeutic potential.-Serhan,
C. N. Treating inflammation and infection in the 21st century: new hints from
decoding resolution mediators and mechanisms.
|Animals
[MESH]
|Anti-Inflammatory Agents/*pharmacology/therapeutic use
[MESH]