New Insights in Mast Cell Modulation by Palmitoylethanolamide
was the title of a review of drs De Filippis, Iuvone and collaegues in CNS & Neurological Disorders – Drug Targets, 2013, 12, 78-83.
The authors discussed the findings of prof. Levi-Montalcini and the mechanism proposed by her group to explain PEA action, first identified in the 1990s, the so called ALIA mechanism or the “Autacoid Local Inflammation Antagonism”. They pointed out that later this terminology was modified into “Autacoid Local Injury Antagonism”.
The change in acronym was based on the observation that “the pharmacological effects of PEA appear to reflect the consequences of supplying the tissue with a sufficient quantity of its physiological regulators of cellular homeostasis” (Aloe, L.; Leon, A.; Levi-Montalcini, R. A proposed autacoids mechanism controlling mastocyte behavior. Agents Actions 1993; 39: C145-7). Thus, De Fillipis et al point out that
PEA needs to be being viewed as a broad bioactive “protector” instead of limiting its field of action to the inflammation response.
The authors also commented on the clinical findings related to PEA, after extensively describing all in vitro and in vivo experiments supporting PEA’s biological role in pain and inflammation:
On the basis of encouraging in vitro and in vivo evidence, the effect of PEA was explored also in several clinical trials, both in human and in pet animals, for inflammatory and pain syndromes. It was reported that PEA-based drugs showed no notable side effects; overall, more than 2000 patients have been successfully treated with PEA, with no adverse effects reported in any of the trials.
In their conclusion section the authors refered again to the milestone work of Nobel Laureate Rita Levi-Montalcini:
“Since its discovery and even before the understanding of its multi-target mechanism of action, PEA was considered as an endogenous compound able to negatively modulate the inflammatory process. As suggested for the first time by the Nobel Laureate Rita Levi Montalcini, there is a strong correlation between MC and PEA anti-inflammatory actions; for this reason, the term “ALIAmide” was coined to define PEA.
An ALIAmide is an autocoid synthesized and released in response to injury or inflammation acting locally on MCs to counteract the pathological event. This definition fits well the PEA mode of action.” To conclude with:
Since its discovery, the effects of PEA have been extensively investigated in in vitro, in vivo and in clinical studies. While discrepancies remain, the efficacy of PEA to control mast cell behaviour is now well- recognized by the scientific community.