interleukin-8 and Dermatitis-Herpetiformis

Topics: Adult; Aged; Aged, 80 and over; Chemokines; Cytokines; Dermatitis Herpetiformis; GTP-Binding Proteins; Humans; Immunoglobulin A; Interferon-gamma; Interleukin-12; Interleukin-13; Interleukin-4; Interleukin-5; Interleukin-8; Male; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease in which antigen presentation in the gastrointestinal mucosa results in cutaneous IgA deposition and distinct, neutrophil-driven cutaneous lesions. Our findings suggest that the qualitatively different immune response to gluten in the intestinal mucosa of patients with DH results in minimal clinical symptoms, allowing the continued ingestion of gluten and the eventual development of DH. Our model may provide a new way to understand the pathogenesis of other skin diseases associated with gastrointestinal inflammation such as pyoderma gangrenosum or erythema nodosum, or explain association of seronegative inflammatory arthritis with inflammatory bowel disease.

Topics: Animals; Celiac Disease; Dermatitis Herpetiformis; Diet, Gluten-Free; Humans; Immunity, Mucosal; Immunoglobulin A; Inflammation Mediators; Interleukin-8; Models, Biological; Skin; Tumor Necrosis Factor-alpha

Patients with dermatitis herpetiformis (DH) have a gluten-sensitive enteropathy and while on gluten-containing diets have elevated levels of serum IL-8. We hypothesized that the mucosal immune response to gluten is responsible for the elevated serum IL-8. Six DH patients were studied while on a gluten-free diet (GFD), whereas four continued on a normal diet. Patients were followed for a mean 2.2 years and serum IL-8 was analyzed. Small bowel biopsies from five DH patients on normal diets, two DH patients on GFD, and six subjects with no small bowel abnormalities were analyzed for IL-8 mRNA. Serum IL-8 levels normalized in five of six patients on GFD and decreased in one, whereas serum IL-8 levels showed no statistically significant change in DH patients on normal diets. Small bowel biopsies from DH patients on normal diets had increased expression of IL-8 mRNA compared to normal subjects, whereas patients on a GFD showed no significant increase in small bowel mRNA. No significant IL-8 mRNA was detected in normal skin biopsies from patients with DH. These observations suggest that the IL-8 in the serum of patients with DH originates from the small bowel as a mucosal immune response to gluten ingestion.

Topics: Adult; Aged; Biopsy; Celiac Disease; Dermatitis Herpetiformis; Diet; Female; Glutens; Humans; Immunoglobulin A; Interleukin-8; Intestine, Small; Male; Middle Aged; RNA, Messenger

The mechanisms that lead to the development of skin lesions in patients with dermatitis herpetiformis (DH) are not known. We hypothesized that an ongoing immune response in the gut of patients with DH would result in an increase in circulating cytokines and be associated with endothelial cell activation, creating a proinflammatory environment in the skin. Skin biopsies from the normal-appearing inner arm of 11 DH patients, with no active skin lesions, and 12 normal subjects were analyzed for E-selectin (E-sel) and ICAM-1 mRNA. DH patients' skin expressed markedly increased levels of E-sel mRNA. Mean E-sel mRNA expression in DH skin was 1,271 (range 63.78-5861) times greater than that of a control, normal skin (P<0.001) with no significant increased expression of ICAM-1 mRNA. Serum levels of soluble E-selectin (sE-sel), IgA anti-tissue transglutaminase antibodies, and serum IL-8 levels were significantly increased in patients with DH. These studies demonstrate that patients with DH have evidence of endothelial cell activation in the skin and systemic manifestations of the ongoing inflammation associated with the mucosal immune response. Endothelial cell activation may play a critical role in the development of skin lesions in patients with DH and may represent a common mechanism for cutaneous manifestations of inflammatory gastrointestinal diseases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dermatitis Herpetiformis; E-Selectin; Endothelial Cells; Female; Gastroenteritis; GTP-Binding Proteins; Humans; Immunoglobulin A; Intercellular Adhesion Molecule-1; Interleukin-8; L-Selectin; Male; Middle Aged; Protein Glutamine gamma Glutamyltransferase 2; RNA, Messenger; Skin; Transglutaminases; Tumor Necrosis Factor-alpha

In autoimmune bullous skin diseases, accumulation of neutrophils and/or eosinophils in the affected skin represents a characteristic feature. So far, however, the induction of this granulocyte infiltration has not been elucidated.. Regarding their biological effects, the chemokines interleukin 8 (IL-8) and RANTES (regulated upon activation normal T lymphocyte expressed and secreted) could play a role in this granulocyte accumulation.. Immunohistochemical examination of lesional skin from patients with bullous pemphigoid, pemphigus, dermatitis herpetiformis and linear IgA disease was performed using a set of different antibodies against IL-8 and RANTES. Additionally, blister fluids were screened for soluble RANTES peptide using an ELISA.. No difference in chemokine expression was found in lesions of autoimmune bullous diseases compared to normal skin.. In contrast to chronic inflammatory diseases like psoriasis and eczema, where keratinocyte IL-8 immunoreactivity was found to differ from normal skin, keratinocyte immunoreactivity is not altered in autoimmune bullous diseases.

Topics: Autoimmune Diseases; Blister; Chemokine CCL5; Dermatitis Herpetiformis; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin A; Immunohistochemistry; Interleukin-8; Pemphigoid, Bullous; Pemphigus; Skin; Skin Diseases, Vesiculobullous

The infiltration of polymorphonuclear neutrophils (PMN) into the upper dermis which characterizes the skin lesions of dermatitis herpetiformis (DH) has never been satisfactorily explained. This study has shown that lesional skin of patients with DH has increased expression of endothelial leucocyte adhesion molecules (ELAM) in the deep dermis, combined with a markedly increased staining for interleukin 8 (IL-8) in the basal epidermal layer. Dendritic cells which stained for granulocyte macrophage colony stimulating factor (GM-CSF) were also observed at the dermo-epidermal junction, and this phenomenon was more pronounced in lesional than in uninvolved DH skin. ELAM, IL-8 and GM-CSF are known to promote infiltration and activation of PMN, and it is suggested that these cytokines may play a key role in the generation of DH lesions.

Topics: Adult; Cell Adhesion Molecules; Cytokines; Dermatitis Herpetiformis; E-Selectin; Epidermis; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunohistochemistry; Interleukin-8; Keratinocytes; Neutrophils; Skin