Mast cells are immune cells found in tissues throughout the body that play an important role in allergic reactions and modulating the immune response. They respond to triggers like pathogens, allergens, and physiological stress by releasing chemical mediators that cause inflammation. Under normal conditions, mast cell responses are regulated by endogenous fatty acid amides through a negative feedback loop. However, during persistent physiological stress this regulation can fail, leading to uncontrolled mast cell degranulation and potential tissue damage. Adelmidrol is a fatty acid amide analogue that acts through the same regulatory mechanism to control mast cell responses and restore homeostasis during periods of stress.

2. Mast cells are immune cells which line the surfaces of the body including the skin, the
respiratory, gastro-intestinal and genito-urinary tracts1. They are in a prime position to
recognise and counter foreign antigens, pathogens or toxins1, and play an important role in
the modulation of an appropriate immune response2.
Mast cells respond to a number of triggers including pathogens (bacterial, fungal, viral),
allergens, proteins (cytokines, growth factors and hormones) and other triggers (radioactivity,
drugs, trauma)3.
Mast cells are involved in allergic reactions, during which degranulation leads to release of
chemical mediators including histamine and cytokines4, resulting in an immune response
and inflammation. Mast cells are also able to synthesise and release specific mediators
in response to pathogens and other triggers without degranulation4,5. Mast cells play an
immunomodulatory role, influencing the immune response as a whole (inflammation, tissue
remodelling and wound healing) and specifically the mast cell response1.
Selective and
controlled
degranulation
Normal Stimulation Trigger
Endogenous fatty
acid amides
The mast cell response is regulated at a local level by endogenous chemicals or autocoids,
in particular fatty acid amides, which control the mast cell response via a negative feedback
loop6. This process is known as autocoid local injury antagonism (ALIA)6.
Controlled release of:
Histamine
Serotonin
Proteases
Nerve growth factor (NGF)
Nitrous oxide (NO)
Normal tissue reaction
Interleukin
Tumour necrosis factor- (TNF- )
Vascular endothelial growth factor (VEGF)
Other mediators

3. During persistent physiological stress, the release of chemical mediators from mast cells
can become uncontrolled7. This is due to a lack of endogenous fatty acid amides resulting in
an uncontrolled release of non-specific mediators from hyper-reactive mast cells leading to
inflammation and potential tissue damage8.
Non-selective
and uncontrolled
degranulation
Physiological stress
(radiotherapy, chemotherapy,
Excess stimulation heat, trauma, infection,
hormonal changes)
Uncontrolled release of: De-epithelialisation
Changes in connective tissue
Erythema
Histamine
Oedema/swelling
Serotonin
Erosion
Proteases
Ulcer
NGF
Desquamative changes
NO
Itching
Interleukin
Burning
TNF-
Dryness
VEGF
Pain
Other mediators
Development of chronic disease
Atrophy
Oxidative damage
Loss of resistance/elasticity
Hyperalgesia

4. In order to avoid potential tissue damage resulting from persistent physiological stress, it is
important to regulate the hyper-reactive mast cell and regain homeostasis1.
Adelmidrol is a fatty acid amide analogue which acts via the ALIA mechanism to regulate
mast cell response to stimuli9.
Adelmidrol modulates the mast cell reaction by controlling the release of chemical mediators
and regaining homeostasis10-13.
Selective and
controlled
degranulation
Physiological stress
(radiotherapy, chemotherapy,
Excess stimulation heat, trauma, infection,
hormonal changes)
Adelmidrol
Controlled release of:
Histamine
Serotonin
Proteases
NGF Restoration of a
NO normal tissue reaction
Interleukin
TNF-
VEGF
Other mediators

5. Adelmidrol from AgainLife
For skin problems
DerLife For inflamed, red, desquamated and/or dehydrated skin in patients undergoing
radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.
milk and cream
30 ml 100 ml
RaLife For skin changes, including itching, irritation and redness, in patients undergoing
radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.
milk and cream
30 ml 100 ml
ClinLife To combat osmidrosis (foul smelling sweat) and/or bromhidrosis (excessive sweating) in
patients with cancer receiving radiation and/or chemotherapy.
milk and cream
30 ml 100 ml
For muco-genital problems
EvaLife For the treatment of itching, burning, redness and dryness of the vulva and vagina
in patients undergoing radiation or chemotherapy and in patients with burns, post-septic
gel and wash
or post-surgical stress.
30 ml 100 ml
HomoLife For the treatment of itching, burning, redness and dryness of the foreskin and penis in
patients undergoing radiation or chemotherapy, and in patients with burns, post-septic,
gel and wash
post-surgical stress or after instrumental manoeuvres.
30 ml 100 ml
GutLife For the treatment of skin/mucosal changes (itching, burning, redness, swelling and
tenderness) in the anal and peri-anal area in patients undergoing radiation or
ointment
chemotherapy and in patients with burns, post-septic or post-surgical stress.
30 ml
For nail and hair problems
OnicoLife For the treatment of tender and/or fragile nails in patients undergoing radiation or
chemotherapy and in patients with burns, post-septic or post-surgical stress. May also be
drops
useful for onychorrhexis (longnitudinal nail ridges), onychoschizia (split nails), xanthonychia
(yellowed nails), melanonychia (blackened nails) and onychocryptosis (ingrown nails).
15 ml
OnicoLife For the treatment of paronychia (skin infection around the nail) in patients undergoing
radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.
gel
5 ml
ZerLife For the treatment of changes in hair growth (fragile hair or hair loss) caused by
radiation, chemotherapy or environmental stress.
shampoo and lotion
100 ml 100 ml
For oral mucosa problems
OraLife For the treatment of red, painful, swollen and/or dry oral mucosa in patients undergoing
radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.
mouthwash and gel
30 ml 100 ml
TraLife For the treatment of the oropharyngeal cavity in patients undergoing radiation or
chemotherapy and in patients with burns, post-septic or post-surgical stress.
spray
30 ml

6. References
1. Galli SJ, Grimbaldeston M, Tsai M. Immunomodulatory mast 8. Re G, Barbero R, Miolo A et al. Palmitoylethanolamide,
cells: negative, as well as positive, regulators of immunity. Nat endocannabinoids and related cannabimimetic compounds
Rev Immunol 2008;8(6):478-486. in protection against tissue inflammation and pain: potential
use in companion animals. Vet J 2007;173(1):21-30.
2. Abraham SN, St John AL. Mast cell-orchestrated immunity to
pathogens. Nat Rev Immunol 2010;10(6):440-452. 9. De Filippis D, D’ mico A, Cinelli MP et al. Adelmidrol, a
A
palmitoylethanolamide analogue, reduces chronic inflammation
3. Moon TC, St Laurent CD, Morris KE et al. Advances in mast in a carrageenin-granuloma model in rats. J Cell Mol Med
cell biology: new understanding of heterogeneity and function. 2009;13(6):1086-1095.
Mucosal Immunol 2010;3(2):111-128.
10. Micali G, Pulvirenti N, Musumeci ML et al. Topical adelmidrol
4. Theoharides TC, Kempuraj D, Tagen M et al. Differential 2% emulsion, a novel aliamide, in the treatment of mild atopic
release of mast cell mediators and the pathogenesis of dermatitis in pediatric subjects: a pilot study. J Am Acad
inflammation. Immunol Rev 2007;217:65-78. Dermatol 2006; 54 (3): Suppl AB112.
5. Galli SJ, Tsai M. Mast cells: versatile regulators of inflammation, 11. Pulvirenti N, Nasca MR, Micali G. Topical adelmidrol 2%
tissue remodeling, host defense and homeostasis. J Dermatol emulsion, a novel aliamide, in the treatment of mild atopic
Sci 2008;49(1):7-19. dermatitis in pediatric subjects: a pilot study. Acta
Dermatovenerol Croat 2007;15(2):80-83.
6. Aloe L, Leon A, Levi-Montalcini R. A proposed autacoid
mechanism controlling mastocyte behaviour. Agents Actions 12. Bonello D, Squarzoni P. Effect of a mucoadhesive gel and
1993;39 Spec No:C145-7. dental scaling on gingivitis in dogs. J Vet Dent 2008;25(1):28-32.
7. Harvima IT, Nilsson G, Naukkarinen A. Role of mast cells and 13. Abramo F, Sailuzzi D, Leotta R et al. Mast cell morphometry
sensory nerves in skin inflammation. G Ital Dermatol Venereol and densitimetry in experimental skin wounds treated with
2010;145(2):195-204. a gel containing adelmidrol: a placebo controlled study.
Wounds 2008;20(6):149-157.
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