vasoactive-intestinal-peptide and Dermatitis--Allergic-Contact

Vasoactive intestinal polypeptide (VIP) is a neuropeptide with immunomodulatory properties. To elucidate the possible role of VIP in the pathophysiology of cutaneous contact hypersensitivity, we compared involved with uninvolved skin of allergic contact dermatitis (ACD) from nickel-allergic patients. Assays included quantification of VIP-immunoreactive (VIP-IR) nerve fibres and cells bearing immunoreactivity for VIP1 and VIP2 receptors in skin biopsy specimens, and of the concentration of VIP-like immunoreactivity (VIP-LI) in extracts of biopsy specimens. VIP-IR nerve fibres were found in the deeper part of the dermis close to sweat glands and hair follicles. No difference in the presence of VIP-IR nerve fibres was found between involved and uninvolved skin of ACD. VIP1 and VIP2 receptor immunoreactivity was seen on keratinocytes in the basal layer of the epidermis, with no difference between involved and uninvolved skin. Staining was also seen on vessel walls and mononuclear cells in the dermis. The highest staining intensity in the mononuclear cells was noted with the antibodies against the VIP2 receptor. While most of the mononuclear cells were stained in uninvolved skin, a minority of the cells showed a positive signal in involved skin. The concentration of VIP-LI in uninvolved skin was 1.53+/-0.790 pmol/g and in involved skin 1.41+/-0.735 pmol/g. It is concluded that there is no significant difference in either the distribution of VIP-IR fibres or the concentration of VIP-LI between involved and uninvolved skin of ACD. However, the number of dermal mononuclear cells showing VIP2 receptor immunoreactivity in skin of ACD was reduced.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Dermatitis, Allergic Contact; Female; Humans; Immunohistochemistry; Middle Aged; Radioimmunoassay; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Skin; Vasoactive Intestinal Peptide

There is increasing evidence that the nervous system has influence on the immune response. The effect of vasoactive intestinal peptide (VIP) and of serotonin and its antagonists on the challenge phase of allergic contact dermatitis in humans were tested. The substances were injected intracutaneously shortly before and 6 h after application of patch tests with nickel sulphate in nickel-allergic patients and the test areas were measured after a further 18 h. Biopsy specimens were also taken for immunohistochemistry. The diameter of the nickel sulphate-induced test reaction was significantly reduced after injection of VIP at 10(-6)-10(-5) mol/l, but was not affected by serotonin or ketanserin. Also tested was the influence of the substances on the response of peripheral blood mononuclear cells from nickel-allergic subjects to nickel sulphate, when added at the same time as the antigen. No effect on the cell proliferative rate was seen, except for an inhibitory effect of serotonin and its antagonists at 10(-5)-10(-4) mol/l. VIP, at 10(-5) mol/l and serotonin at 10(-4) mol/l stimulated the secretion of interferon gamma. The interleukin-2 soluble receptor secretion was slightly stimulated by 5-HT at 10(-4) mol/l and by ketanserin at 10(-6) mol/l. In conclusion, our results show that when injected intracutaneously in the challenge phase of allergic contact dermatitis, VIP has an inhibitory effect, which might be explained by enhanced leukocyte production of interferon gamma.

Topics: Adult; CD4 Antigens; Cell Division; Dermatitis, Allergic Contact; DNA; Female; HLA-DR Antigens; Humans; Immunohistochemistry; Interferon-gamma; Interleukin-2; Interleukin-4; Ketanserin; Leukocytes, Mononuclear; Male; Middle Aged; Nickel; Receptors, Interleukin-2; Serotonin; Skin; Vasoactive Intestinal Peptide

Neuromediators may influence the immune response. To investigate their potential immunomodulating role in established allergic contact dermatitis in man, the following neuromediators were tested: vasoactive intestinal polypeptide (VIP), serotonin, and the serotonin antagonists ketanserin, methiotepine and ICS-205-930. Positive patch test reactions were elicited by application of nickel sulphate for 48 h. The neuromediators were applied under patch test conditions after another 24 h. The test areas were measured before and 24 h after application of the neuromediators and biopsy specimens were taken for immunohistochemistry. After application of VIP at a concentration of 10(-5) mol/l, and of ketanserin at a concentration of 10(-4) mol/l, there was a significant reduction in the diameter of the test reaction. In addition, with VIP there was a reduction in the number of Leu 3a+ cells. Also tested was the influence of the neuromediators on the proliferative response of peripheral blood mononuclear cells from nickel-allergic subjects to nickel sulphate. The cells were cultured for 6 days and the neuromediators were added after 3 days. There was no effect on the proliferative response, except for slight inhibition by serotonin and by ketanserin at 10(-4) mol/l. More interferon gamma was found in the supernatants when VIP was added at 10(-5) and 10(-6) mol/l than in the control cultures. Thus, VIP and ketanserin may have an inhibitory effect on established allergic contact dermatitis. The effect of VIP is possibly mediated by an increased production of interferon gamma.

Topics: Adjuvants, Immunologic; Cells, Cultured; Dermatitis, Allergic Contact; DNA; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Indoles; Interferon-gamma; Interleukin-2; Ketanserin; Lymphocyte Activation; Methiothepin; Nickel; Patch Tests; Receptors, Interleukin-2; Serotonin; Serotonin Antagonists; Tropisetron; Vasoactive Intestinal Peptide

There is increasing evidence indicating that the nervous system influences the immune response. In the present study the potential immunomodulatory role of vasoactive intestinal polypeptide (VIP) in established allergic contact dermatitis in humans was investigated. Positive patch-test reactions were elicited by application of nickel sulphate for 48 h. VIP was applied under patch-test conditions after another 24-h period. The test areas were measured before and 24 h after application of VIP and biopsy specimens were taken for immunohistochemistry. After application of VIP at 10(-5) mol/L, there was a significant reduction in the diameter of the test reaction. In addition, there was a reduction in the number of Leu 3a+ cells. The influence of VIP on the proliferative response of peripheral blood mononuclear cells from nickel-allergic subjects to nickel sulphate was also tested. The cells were cultured for 6 days and VIP was added after 3 days. There was no effect on the proliferative response. However, when VIP was added at 10(-6) and 10(-5) mol/L, a higher level of interferon gamma was found in the nickel-treated cell cultures compared to the controls. In conclusion, VIP may have an inhibitory effect on established allergic contact dermatitis. This inhibitory effect is possibly mediated through an increased production of interferon gamma by peripheral blood mononuclear cells.

Topics: Biopsy; Cells, Cultured; Dermatitis, Allergic Contact; Female; Humans; Interferon-gamma; Lymphocyte Activation; Lymphocytes; Nickel; Skin; Skin Tests; Vasoactive Intestinal Peptide