interleukin-8 and Pyoderma-Gangrenosum

Topics: Administration, Cutaneous; Aged; Diverticulitis, Colonic; Female; Humans; Ileostomy; Interleukin-8; Ointment Bases; Postoperative Complications; Pyoderma Gangrenosum; Skin; Tacrolimus; Treatment Outcome

Topics: Antineoplastic Agents, Phytogenic; C-Reactive Protein; Chromosomes, Human, Pair 8; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Middle Aged; Myelodysplastic Syndromes; Prothrombin Time; Pyoderma Gangrenosum; Trisomy

A 12-year-old male entire Miniature Pinscher presented with excoriations at various body sites, progressively forming ulcers and enlarging until arrested by treatment. Based on the clinical presentation and histopathological analyses, sterile neutrophilic dermatosis was suspected. Therefore, the dog was started on prednisolone. Marked improvement was achieved with prednisolone treatment, suggesting a diagnosis of pyoderma gangrenosum (PG). Transcription levels of cytokine mRNA in lesional skin before and after treatment from this dog were quantified by real-time RT-PCR. Transcription levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-8 and IL-17A were higher in lesional skin before treatment than after treatment. Levels of various cytokines could be increased in lesional skin of dogs with PG as well as in human patients with PG.

Topics: Animals; Dog Diseases; Dogs; Interleukin-17; Interleukin-1beta; Interleukin-8; Male; Pyoderma Gangrenosum; Real-Time Polymerase Chain Reaction; Skin; Tumor Necrosis Factor-alpha

Pyoderma gangrenosum (PG) and Sweet's syndrome (SS) are two inflammatory skin diseases presenting with painful ulcers and erythematous plaques, respectively; both disorders have a debilitating clinical behaviour and PG is potentially life-threatening. Recently, PG and SS have been included among the autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. However, an autoinflammatory pattern clearly supporting this inclusion has never been demonstrated. We studied 16 patients with PG, six with SS and six controls, evaluating, using a sandwich-based protein antibody array method, the expression profile of inflammatory effector molecules in PG, SS and normal skin. The expressions of interleukin (IL)-1 beta and its receptor I were significantly higher in PG (P = 0·0001 for both) and SS (P = 0·004-0·040) than in controls. In PG, chemokines such as IL-8 (P = 0·0001), chemokine (C-X-C motif) ligand (CXCL) 1/2/3 (P = 0·002), CXCL 16 (P = 0·003) and regulated upon activation normal T cell expressed and secreted (RANTES) (P = 0·005) were over-expressed. In SS, IL-8 (P = 0·018), CXCL 1/2/3 (P = 0·006) and CXCL 16 (P = 0·036) but not RANTES were over-expressed, suggesting that chemokine-mediated signals are lower than in PG. Fas/Fas ligand and CD40/CD40 ligand systems were over-expressed in PG (P = 0·0001 for Fas, P = 0·009 for Fas ligand, P = 0·012 for CD40, P = 0·0001 for CD40 ligand), contributing to tissue damage and inflammation, while their role seems to be less significant in SS. Over-expression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that PG and SS are autoinflammatory diseases. The differences in expression profile of inflammatory effectors between these two disorders may explain the stronger local aggressiveness in PG than SS.

Topics: Adolescent; Adult; Aged; CD40 Antigens; Chemokines, CXC; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-8; Ligands; Male; Middle Aged; Pyoderma Gangrenosum; Sweet Syndrome; T-Lymphocytes

Pyoderma gangrenosum (PG) is a rare, immune-mediated inflammatory skin disease presenting with painful ulcers having undermined edges. Less commonly, bullous and vegetative variants exist. Histology consists of a neutrophil-rich dermal infiltrate. We characterized immunohistochemically the infiltrate in different variants of PG and in another neutrophilic dermatosis as Sweet's syndrome. We studied 21 patients with PG, eight with Sweet's syndrome and 20 controls, evaluating skin immunoreactivity for inflammatory cell markers (CD3, CD163 and myeloperoxidase), cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-8 and IL-17], metalloproteinases (MMP-2 and MMP-9) and vascular endothelial growth factor (VEGF). Immunoreactivities of CD3, CD163, myeloperoxidase, TNF-α, IL-8, IL-17, MMP-2, MMP-9 and VEGF were significantly higher in both PG and Sweet's syndrome than in controls (P=0·0001). Myeloperoxidase (neutrophil marker), IL-8 (cytokine chemotactic for neutrophils) and MMP-9 (proteinase-mediating tissue damage) were expressed more significantly in both ulcerative and bullous PG than in vegetative PG as well as in Sweet's syndrome (P=0·008-P=0·0001). In ulcerative PG, the expression of CD3 (panT cell marker) and CD163 (macrophage marker) were significantly higher in wound edge than wound bed (P=0·0001). In contrast, the neutrophil marker myeloperoxidase was expressed more significantly in wound bed than wound edge (P=0·0001). Our study identifies PG as a paradigm of neutrophil-mediated inflammation, with proinflammatory cytokines/chemokines and MMPs acting as important effectors for the tissue damage, particularly in ulcerative and bullous PG where damage is stronger. In ulcerative PG, the wound bed is the site of neutrophil-recruitment, whereas in the wound edge activated T lymphocytes and macrophages pave the way to ulcer formation.

Topics: Adolescent; Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; CD3 Complex; Cytokines; Female; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-17; Interleukin-8; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Middle Aged; Neutrophils; Peroxidase; Pyoderma Gangrenosum; Receptors, Cell Surface; Sweet Syndrome; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Young Adult

Topics: Adsorption; Antibodies; Blood Component Removal; Colitis, Ulcerative; Granulocytes; Head; Humans; Interleukin-6; Interleukin-8; Male; Monocytes; Phosphatidylserines; Prothrombin; Pyoderma Gangrenosum; Young Adult

Topics: Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Breast Diseases; Colitis, Ulcerative; Female; Humans; Interleukin-8; Mesalamine; Pyoderma Gangrenosum; Treatment Outcome

We here present the case of a 5-yr-old girl with pyoderma gangrenosum (PG) in association with underlying CD30+ anaplastic large cell lymphoma with increased serum cytokine levels (interleukin-8, granulocyte colony-stimulating factor). An association between PG and increased cytokine levels was suggested. Even in children, dermatosis of PG should receive prompt careful evaluation for underlying hematological malignancy.

Topics: Child, Preschool; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Ki-1 Antigen; Lymphoma, Large B-Cell, Diffuse; Osteolysis; Pyoderma Gangrenosum

Topics: Adult; Colitis, Ulcerative; Escherichia coli Infections; Female; Humans; Interleukin-8; Pyoderma Gangrenosum

Interleukin-8 (IL-8) is a potent chemotactic polypeptide for neutrophils. However, the role of this cytokine during inflammation remains unclear. Skin specimens from patients with pyoderma gangrenosum demonstrated IL-8 overexpression in skin ulcers, which suggests a role for IL-8 in the development of the disease. We therefore constructed a recombinant adenovirus expressing the complementary deoxyribonucleic acid encoding human IL-8 (IL-8/Ad5) that induces a 2000-fold increase in IL-8 expression of infected human fibroblasts in vitro. Human skin engrafted to severe combined immunodeficiency mice and then injected with the recombinant virus demonstrated erythema, an intense perivascular infiltration of neutrophils, and extravasation of erythrocytes after 8 hours. By 12 hours after injection, neutrophils had accumulated beneath the epidermis, which then necrotized, and one or more ulcers that remained for approximately 2 weeks were observed. Clinically and histologically, the ulcers resembled pyoderma gangrenosum. These clinical and experimental findings suggest an etiologic role of IL-8 in the pathogenesis of pyoderma gangrenosum.

Topics: Animals; Gene Expression Regulation; Humans; Interleukin-8; Mice; Mice, SCID; Pyoderma Gangrenosum; Recombinant Proteins; Skin; Skin Transplantation; Transplantation, Heterologous; Ulcer