Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in miceReportar como inadecuado

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Arthritis Research and Therapy

, 15:4055

First Online: 18 November 2013Received: 17 July 2013Accepted: 04 November 2013


IntroductionN-palmitoylethanolamine PEA is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines NAEs. Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis CIA.

MethodsCIA was induced by an intradermally injection of 100 μl of the emulsion containing 100 μg of bovine type II collagen CII and complete Freund adjuvant CFA at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA 10 mg-kg 10% ethanol, intraperitoneally i.p. or co-ultramicronized PEA + luteolin 1 mg-kg, i.p. every 24 hours, starting from day 25 to 35.

ResultsMice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde MDA levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment.

ConclusionsWe demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.

AbbreviationsCFAComplete Freund adjuvant

CIAType II collagen-induced arthritis

CIICollagen type II




MCMast cell


NF-κBNuclear factor-κB


RARheumatoid arthritis

ROSReactive oxygen species

TNF-αTumor necrosis factor-α.

An erratum to this article can be found at

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Autor: Daniela Impellizzeri - Emanuela Esposito - Rosanna Di Paola - Akbar Ahmad - Michela Campolo - Angelo Peli - Valeria Maria 


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