title: Leukocyte infiltration and mRNA expression of IL-20, IL-8 and TNF-R P60 in psoriatic skin is driven by TNF-alpha.
abstract: Anti-TNF-alpha therapy with a chimeric monoclonal antibody (Infliximab, Remicade) has been shown to be highly effective in the treatment of skin lesions as well as arthritis in patients with psoriatic arthritis. In this study we investigated the molecular consequences of the in vivo TNF-alpha blockade with infliximab in psoriatic skin lesions of 6 patients with severe psoriatic arthritis. Biopsies from lesional and non-lesional skin were taken before and 10 weeks after the initiation of treatment. Immunohistochemistry and semiquantative RT-PCR were performed focusing on proinflammatory gene products. Immunohistochemistry, after three infusions, revealed a marked decrease in the expression of TNF-alpha, HLA-DR, CD3, CD15, ICAM-1 and LFA-1 positive cells. By semiquantitative RT-PCR, we analysed mRNA expression of IL-8, IL-20, TNF-R (TNF-R p60 and TNF-R p80), IL-1R I and IL-1R II, as well as ICAM-2. Before therapy, m-RNA for IL-8, IL-20, TNF-R p60, TNF-R p80, IL-1R II and ICAM-2 were detected in lesional skin. mRNA expression of IL-8 and IL-20 completely disappeared and mRNA expression of TNF-R p60 was reduced after therapy. This effect on IL-8 expression was paralleled by a decreased infiltration of leukocytes in psoriatic skin. These data suggest that the clinical response of anti-TNF-alpha therapy in patients with psoriasis or psoriatic arthritis may be, at least in part, caused by the inhibition of the production of proinflammatory cytokines and by the decreased expression of adhesion molecules with the consequence of an impaired migration of proinflammatory cells into the inflamed tissue. These data further support a critical role for TNF-alpha in the pathology of psoriasis.
authors.affiliation: Department of Dermatology, University Hospital of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: A L J
authors.initials: AL
authors.lastname: Ogilvie
authors.forename: M
authors.initials: M
authors.lastname: Lüftl
authors.forename: C
authors.initials: C
authors.lastname: Antoni
authors.forename: G
authors.initials: G
authors.lastname: Schuler
authors.forename: J R
authors.initials: JR
authors.lastname: Kalden
authors.forename: H M
authors.initials: HM
authors.lastname: Lorenz
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D016209:Interleukin-8 / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis*; D007962:Leukocytes / Q000378:metabolism*; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000096:biosynthesis*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016209:Interleukin-8; D007378:Interleukins; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; C422042:interleukin 20