Study of serotonin, innervation and sensory neuropeptides in allergic contact dermatitis

In a murine model of contact allergy, 24 h after challenge with antigen, increased axonal growth using an antibody to growth-associated protein-43 (GAP-43) was seen in the epidermis and dermis of eczematous skin. Protein gene product 9.5 (PGP 9.5) positive nerve fibres tended to increase in the eczematous skin. There was also a higher number of galanin and a tendency to a higher number of calcitonin gene-related peptide (CGRP) and substance P positive fibres. In contrast, the concentrations of galanin and CGRP were lower and substance P concentration tended to decrease. Serotonin positive platelets were also increased in the eczematous skin.

Expression of 5-HT2C receptor (R) was seen on murine epidermal dendritic, I-A positive cells, being more numerous in the eczematous than in the control skin. With the 5-HT2CR agonist (RO 60-0175/007), at high concentrations, and the murine XS52 Langerhans celllike line, there was an increased IL- 1beta production, by using ELISA.

In human positive epicutaneous patch test reactions, at 72h, an increased number of GAP43 immunoreactive nerve fibres were found in the eczematous compared to control skin. Semiquantification showed an increase in dermal substance P and its neurokinin 1 receptor positive inflammatory mononuclear cells. Serotonin positive platelets were increased in the eczematous skin. A decrease in the number of 5-HT1AR positive cells, the majority being mast cells, was seen in the eczematous compared to control skin. Contrariwise, both 5HT2AR, being CD3, CD4 or CD8 positive cells, and serotonin transporter protein (SERT) positive cells, being CD1a, CD4, CD8 positive or CD56+ CD3- cells, were increased. 5-HT3R immunoreactivity was seen in the basal epidermis of the inflamed and control skin. A high concentration of the 5-HT2AR agonist DOI inhibited the proliferation and tended to inhibit the interleukin (IL)-2 production of nickelstimulated peripheral blood mononuclear cells from nickel-allergic patients. A tendency to an inhibition of IL-1beta production from the XS52 cell line was seen by the SERT inhibitors fluoxetine and citalopram at 10-5-10-6 mol/L, respectively.

In conclusion, the serotonergic system, nerve supply and sensory neuropeptides may all be of importance in the pathophysiology of allergic contact dermatitis.

List of scientific papers

I. El-Nour H, Lundeberg L, Boman A, Beck O, Harvima IT, Theodorsson E, Nordlind K (2005). Study of innervation, sensory neuropeptides, and serotonin in murine contact allergic skin. Immunopharmacol Immunotoxicol. 27(1): 67-76.
https://doi.org/10.1081/IPH-200051617

II. El-Nour H, Lundeberg L, Boman A, Theodorsson E, Hokfelt T, Nordlind K (2004). Galanin expression in a murine model of allergic contact dermatitis. Acta Derm Venereol. 84(6): 428-32.
https://doi.org/10.1080/00015550410017290

III. El-Nour H, Lundeberg L, Boman A, Abramowski D, Holst M, Nordlind K (2005). Expression and function of serotonin 2C receptors on murine Langerhans cell-like cells and murine contact allergy. [Submitted]

IV. Lundeberg L, El-Nour H, Mohabbati S, Morales M, Azmitia E, Nordlind K (2002). Expression of serotonin receptors in allergic contact eczematous human skin. Arch Dermatol Res. 294(9): 393-8.
https://doi.org/10.1007/s00403-002-0350-y

V. El-Nour H, Lundeberg L, Al-Tawil R, Granlund A, Abdel-Magid N, Lonne-Rahm SB, Azmitia EC, Nordlind K (2005). Modulation of axonal growth, substance P and serotonin in the human contact allergic reaction. [Submitted]