PMID- 26857391
OWN - NLM
STAT- MEDLINE
DCOM- 20170116
LR  - 20240204
IS  - 1878-7479 (Electronic)
IS  - 1933-7213 (Print)
IS  - 1878-7479 (Linking)
VI  - 13
IP  - 2
DP  - 2016 Apr
TI  - Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse 
      Effects of Interferon-beta1a and Circulating Proinflammatory Cytokines in 
      Relapsing-Remitting Multiple Sclerosis.
PG  - 428-38
LID - 10.1007/s13311-016-0420-z [doi]
AB  - Palmitoylethanolamide (PEA) is an endogenous lipid mediator known to reduce pain 
      and inflammation. However, only limited clinical studies have evaluated the 
      effects of PEA in neuroinflammatory and neurodegenerative diseases. Multiple 
      sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central 
      nervous system. Although subcutaneous administration of interferon (IFN)-beta1a is 
      approved as first-line therapy for the treatment of relapsing-remitting MS 
      (RR-MS), its commonly reported adverse events (AEs) such as pain, myalgia, and 
      erythema at the injection site, deeply affect the quality of life (QoL) of 
      patients with MS. In this randomized, double-blind, placebo-controlled study, we 
      tested the effect of ultramicronized PEA (um-PEA) added to IFN-beta1a in the 
      treatment of clinically defined RR-MS. The primary objectives were to estimate 
      whether, with um-PEA treatment, patients with MS perceived an improvement in pain 
      and a decrease of the erythema width at the IFN-beta1a injection site in addition to 
      an improvement in their QoL. The secondary objectives were to evaluate the 
      effects of um-PEA on circulating interferon-gamma, tumor necrosis factor-alpha, and 
      interleukin-17 serum levels, N-acylethanolamine plasma levels, Expanded 
      Disability Status Scale (EDSS) progression, and safety and tolerability after 1 
      year of treatment. Patients with MS receiving um-PEA perceived an improvement in 
      pain sensation without a reduction of the erythema at the injection site. A 
      significant improvement in QoL was observed. No significant difference was 
      reported in EDSS score, and um-PEA was well tolerated. We found a significant 
      increase of palmitoylethanolamide, anandamide and oleoylethanolamide plasma 
      levels, and a significant reduction of interferon-gamma, tumor necrosis factor-alpha, and 
      interleukin-17 serum profile compared with the placebo group. Our results suggest 
      that um-PEA may be considered as an appropriate add-on therapy for the treatment 
      of IFN-beta1a-related adverse effects in RR-MS.
FAU - Orefice, Nicola S
AU  - Orefice NS
AD  - Department of Pharmacy, "Federico II" University, 80131, Naples, Italy.
FAU - Alhouayek, Mireille
AU  - Alhouayek M
AD  - Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug 
      Research Institute, Universite catholique de Louvain, 1200, Brussels, Belgium.
FAU - Carotenuto, Antonio
AU  - Carotenuto A
AD  - Department of Neurosciences, Reproductive and Odontostomatological Sciences, 
      "Federico II" University of Naples, Naples, Italy.
FAU - Montella, Silvana
AU  - Montella S
AD  - Department of Neurosciences, Reproductive and Odontostomatological Sciences, 
      "Federico II" University of Naples, Naples, Italy.
FAU - Barbato, Franscesco
AU  - Barbato F
AD  - Department of Neurosciences, Reproductive and Odontostomatological Sciences, 
      "Federico II" University of Naples, Naples, Italy.
FAU - Comelli, Albert
AU  - Comelli A
AD  - Department of Biopathology and Medical Biotechnologies, Section of Radiological 
      Sciences, University of Palermo, 90129, Palermo, Italy.
FAU - Calignano, Antonio
AU  - Calignano A
AD  - Department of Pharmacy, "Federico II" University, 80131, Naples, Italy.
FAU - Muccioli, Giulio G
AU  - Muccioli GG
AD  - Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug 
      Research Institute, Universite catholique de Louvain, 1200, Brussels, Belgium.
FAU - Orefice, Giuseppe
AU  - Orefice G
AD  - Department of Neurosciences, Reproductive and Odontostomatological Sciences, 
      "Federico II" University of Naples, Naples, Italy. orefice@unina.it.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurotherapeutics
JT  - Neurotherapeutics : the journal of the American Society for Experimental 
      NeuroTherapeutics
JID - 101290381
RN  - 0 (Amides)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Ethanolamines)
RN  - 0 (Interleukin-17)
RN  - 0 (Palmitic Acids)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 6R8T1UDM3V (palmidrol)
RN  - 82115-62-6 (Interferon-gamma)
RN  - XRO4566Q4R (Interferon beta-1a)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Amides
MH  - Anti-Inflammatory Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Cytokines/*blood
MH  - Disease Progression
MH  - Double-Blind Method
MH  - Ethanolamines/administration & dosage/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Interferon beta-1a/adverse effects/*therapeutic use
MH  - Interferon-gamma/blood
MH  - Interleukin-17/blood
MH  - Male
MH  - Multiple Sclerosis, Relapsing-Remitting/*drug therapy
MH  - Palmitic Acids/administration & dosage/adverse effects/*therapeutic use
MH  - Skin/*drug effects
MH  - Tumor Necrosis Factor-alpha/blood
PMC - PMC4824021
OTO - NOTNLM
OT  - Anandamide
OT  - FAAH
OT  - N-acylethanolamines
OT  - NAAA
OT  - Neuroinflammation
OT  - Oleoylethanolamide
OT  - Pain
EDAT- 2016/02/10 06:00
MHDA- 2017/01/17 06:00
PMCR- 2017/04/01
CRDT- 2016/02/10 06:00
PHST- 2016/02/10 06:00 [entrez]
PHST- 2016/02/10 06:00 [pubmed]
PHST- 2017/01/17 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - S1878-7479(23)01597-0 [pii]
AID - 420 [pii]
AID - 10.1007/s13311-016-0420-z [doi]
PST - ppublish
SO  - Neurotherapeutics. 2016 Apr;13(2):428-38. doi: 10.1007/s13311-016-0420-z.