title: Interleukin-1 in human skin: dysregulation in psoriasis.
abstract: Cytokine dysregulation is an attractive concept to explain many of the observed abnormalities in psoriasis. IL-1, in particular, can potentiate immune cellular activation, activate fibroblasts, and increase endothelial cell adhesiveness to leukocytes. Here, we review IL-1 regulation in normal and psoriatic skin in vivo in relation to normal skin and cultured keratinocytes. Contrary to expectations, IL-1 functional activity in psoriatic lesions is reduced, not increased, relative to normal skin. The reduction is attributable to the presence of IL-1 inhibitors, reduced IL-1alpha levels, and an IL-1beta that lacked function in T-cell assays. IL-1beta protein is actually significantly increased in psoriatic lesions, but the mechanism of its non-functionality remains unclear. Unlike cultured keratinocytes, which accumulate large, inactive IL-1beta precursors, both normal and psoriatic skin process IL-1beta to a mature form. Novel mechanisms of post-translational processing by epidermis in vivo may generate a novel form of IL-1beta with unknown functions. The marked abnormalities of IL-1 regulation in psoriatic skin suggest that this molecule may be important in normal skin homeostasis.
authors.affiliation: Department of Dermatology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Cooper
authors.forename: C
authors.initials: C
authors.lastname: Hammerberg
authors.forename: O
authors.initials: O
authors.lastname: Baadsgaard
authors.forename: J T
authors.initials: JT
authors.lastname: Elder
authors.forename: L S
authors.initials: LS
authors.lastname: Chan
authors.forename: R S
authors.initials: RS
authors.lastname: Taylor
authors.forename: J J
authors.initials: JJ
authors.lastname: Voorhees
authors.forename: G
authors.initials: G
authors.lastname: Fisher
mesh_terms: D006801:Humans; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011565:Psoriasis / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000276:immunology*
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger