interleukin-8 and Pemphigus

The place of cell-mediated immunity and cytokines in the immunopathogenesis of pemphigus vulgaris (PV) has not been fully established.. To assess the serum levels of pro-inflammatory cytokines, Interleukine-6 (IL-6) and Interleukine-8 (IL-8), in PV patients before and after therapy, to evaluate the influence of therapy on the serum cytokine levels.. Sixty-six newly diagnosed PV patients enrolled into the study. The serum levels of IL-8 and IL-6 were measured in 66 and 64 patients, respectively. According to the extent of skin and mucosal involvement, the patients were divided into two groups namely mild and severe. The serum levels of cytokines were measured using enzyme-linked immunosorbent assay (ELISA) method before and after 4 weeks of prednisolone plus azathioprine therapy.. In 64 patients studied for the serum level of IL-6, the median IL-6 level was significantly decreased from 1.6 to 0.9 pg/mL by therapy (P-value = 0.001). Segregating the patients according to the severity of the disease, the serum level of IL-6 did not differ significantly by therapy in patients with a mild disease. However, in patients with a severe disease the median serum level of IL-6 decreased significantly from 1.8 to 0.9 pg/mL after therapy (P-value = 0.001). No significant changes were found in the IL-8 level by treatment.. The significant decrease in the IL-6 level after therapy suggests that blocking of IL-6 could have therapeutic benefits for the treatment of PV, particularly in severe forms.

Topics: Azathioprine; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-6; Interleukin-8; Pemphigus; Prednisolone

Glucocorticoids (GC) represent the main treatment for pemphigus; however, some patients show GC resistance. GC sensitivity was evaluated in 19 pemphigus patients and 41 controls by the number of binding sites [B(max) (fmol/mg protein)] and the affinity of GC receptor [Kd (nM)] to dexamethasone (DEX) as well as by the pattern of cytokine by DEX-mediated inhibition of concanavalin-A (Con-A)-stimulated PBMC proliferation. The Kd (15.7 ± 2.8 vs.8.1 ± 1.3) and Bmax (6.5 ± 0.9 vs. 3.9 ± 0.3) were higher in pemphigus than controls (p = 0.002). Considering the values above the 95th percentile of normal group as a cut-off (K(d) > 24.9 nM and B(max) > 8.1 fmol/mg protein), elevated K(d) and B(max) were observed in 9.8% and 2.4% of controls and 15.8% and 36.8% of patients (p = 0.02). PBMC proliferation was stimulated by Con-A and inhibited by DEX (p < 0.001) in both pemphigus and control groups. IL-6 and TNFα (pg/mL) basal production were higher in patients than controls. There was an increment of these cytokines after Con-A stimulation, and they were inhibited by DEX (p = 0.002) in controls and remained elevated in pemphigus (p < 0.02). Patients and controls showed no difference in basal and stimulated production of IL-8 and IL-10. There is an alteration on GC sensitivity in pemphigus patients and a higher production of proinflammatory cytokines. Therefore, in pemphigus patients, proinflammatory cytokines might be involved in the mechanism of GC resistance and/or in its maintenance.

Topics: Adolescent; Adult; Binding Sites; Concanavalin A; Dexamethasone; Female; Glucocorticoids; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Pemphigus; Protein Binding; Receptors, Glucocorticoid; Tumor Necrosis Factor-alpha; Young Adult

Pemphigus is a chronic auto-immune blistering disease with four main variants, i.e. pemphigus vulgaris (PV), foliaceus (PF), erythematosus (PE) and vegetans. The common histological feature of this disease is acantholysis.. The aim of this study was to compare levels of some cytokines in blister fluid and sera of patients with pemphigus, using as control blister fluid of patients with bullous pemphigoid (BP) and bullous contact dermatitis (BCD).. Using an immuno-enzymatic assay (ELISA), we tested 16 sera and 6 blister fluids of patients with various forms of pemphigus (13 with PV, 1 with PF, 2 with PE), the sera of 16 healthy control subjects, 5 blister fluids of patients with BP and 5 blister fluids of patients with BCD, for the presence of some cytokines (IL-10, IL-8 and IFN-gamma). Intercellular antibodies were searched for and titred; desmoglein 1 and 3 antibody levels were independently evaluated to compare them with the severity of both cutaneous and oral involvement.. The levels of IL-10 in the sera of patients with pemphigus were below the detection limits. IL-8 was significantly increased only in 4 samples of sera from pemphigus patients compared with controls, while IFN-gamma was detected at low levels in almost all patients compared with sera of controls. The cytokine levels in blister fluid of patients with pemphigus were significantly higher than in the sera. There was a difference between the expression of cytokines in blister fluid of control patients with BP and BCD compared with those of pemphigus patients.. This report discusses the anti-inflammatory role played by IL-10 in the chronic form of pemphigus and the hypothesis of a possible role of IL-8 in neutrophil and lymphocyte-monocyte recruitment.

Topics: Adolescent; Adult; Aged; Autoantibodies; Autoantigens; Blister; Body Fluids; Cadherins; Child; Cytokines; Dermatitis, Contact; Desmoglein 1; Desmoglein 3; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-8; Male; Middle Aged; Pemphigus

A subset of pemphigus herpetiformis, a rare pemphigus variant, is characterized histopathologically by subcorneal acantholysis and neutrophilic infiltration. The mechanism of neutrophil infiltration is unknown, but chemokines such as IL-8 may play a role. We investigated the possible role of IL-8 in two such cases. Direct and indirect immunofluorescence studies demonstrated in vivo-bound and circulating IgG epithelial cell surface-binding autoantibodies, both predominated by IgG4 subclass. ELISA and immunoblotting studies revealed that the patients' IgG autoantibodies recognized recombinant desmoglein 1 but not desmoglein 3. Preadsorption of the patients' sera with recombinant desmoglein 1 completely removed the epidermal cell surface immunostaining. Significantly, immunohistochemistry demonstrated intense expression of IL-8, co-localized with in vivo-bound IgG, in the upper epidermis, where the acantholysis took place. Affinity-purified sera IgG from these two patients, a normal individual, and a pemphigus vulgaris patient containing desmoglein 1 autoantibodies, were incubated with normal human keratinocytes in vitro. Cells treated with these patients' IgG secreted a seven-to-nine-fold increase of IL-8 (30-37 pg/ml) compared with the controls (2-4 pg/ml) and expressed a higher intensity of cytoplasmic IL-8 staining. These data demonstrate a novel functional role for IL-8 in the pathogenesis of the neutrophil-dominant subset of pemphigus herpetiformis. The autoantibody-induced epidermal cell IL-8 expression may represent a novel mechanism of epidermal neutrophil recruitment.

Topics: Adult; Aged; Antibody Specificity; Autoantibodies; Cytoskeletal Proteins; Desmoglein 1; Desmoglein 3; Desmogleins; Desmoplakins; Female; Humans; Immunoglobulin G; Interleukin-8; Keratinocytes; Male; Neutrophils; Pemphigus; Skin

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