title: Tumor necrosis factor-alpha and interleukin-1alpha decrease the adherence of Streptococcus pyogenes to cultured keratinocytes.
abstract: We hypothesized that the primary epidermal cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha, which are produced after skin injury, modulate bacterial adherence and the initiation of group A streptococcal skin infections. Streptococcus pyogenes binds preferentially to highly differentiated keratinocytes in vitro, simulating the superficial human skin infection, impetigo, and providing a model system for testing this hypothesis. Exposure of keratinocytes to 10 ng/mL TNF-alpha for 20 h decreased adherence to undifferentiated and differentiated keratinocytes by 33% and 38%, respectively. Treatment with 1 ng/mL IL-1alpha decreased adherence to undifferentiated and differentiated keratinocytes by 23% and 18%, respectively. Exposure to both cytokines simultaneously produced an additive 50% reduction in adherence. These data suggest that TNF-alpha and IL-1alpha may play a role in cutaneous host defense by impeding streptococcal adherence and decreasing its ability to form a nidus of infection in the skin.
authors.affiliation: Divisions of Infectious Diseases, Department of Pediatrics, Division of Dermatology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Darmstadt
authors.forename: P
authors.initials: P
authors.lastname: Fleckman
authors.forename: C E
authors.initials: CE
authors.lastname: Rubens
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D015603:Keratinocytes / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1