title: Intradermal granulocyte-macrophage colony-stimulating factor alters cutaneous antigen-presenting cells and differentially affects local versus distant immunization in humans.
abstract: We hypothesized that intradermal delivery of granulocyte-macrophage colony-stimulating factor (GM-CSF) would alter the number and differentiation state of local antigen-presenting cells and thereby alter immunization strength at that site in humans. GM-CSF or placebo was administered intradermally on consecutive days prior to contact sensitization at that site. In GM-CSF-treated skin, epidermal CD1a(+)S100(+) Langerhans cells were reduced in number and had altered morphology, while the number of dermal CD1a(+), HLA-DR(+), and S100(+) cells was increased. In the deep dermis CD68(+) macrophages were increased. Expression of the APC activation markers CD40 and ICAM-1 was also increased in the dermis. Subjects were sensitized to DNCB through GM-CSF- or placebo-pretreated skin and to DPCP through untreated skin. Subjects immunized through GM-CSF-treated sites exhibited 64% greater elicitation responses to DNCB than placebo-treated subjects. GM-CSF-treated subjects also showed 43% lower responses to DPCP than placebo-treated subjects. The difference between DNCB (local) and DPCP (distant) responses was significantly greater for GM-CSF-treated subjects than for placebo responses (n = 8, P < 0.05). Therefore, local immunization site pretreatment with intradermal GM-CSF enhances immunization efficiency at that site.
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA. kdc@po.cwru.edu
authors.forename: I B
authors.initials: IB
authors.lastname: Kremer
authors.forename: S R
authors.initials: SR
authors.lastname: Stevens
authors.forename: J W
authors.initials: JW
authors.lastname: Gould
authors.forename: J
authors.initials: J
authors.lastname: DiCarlo
authors.forename: G E
authors.initials: GE
authors.lastname: Quinby
authors.forename: K D
authors.initials: KD
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D015415:Biomarkers; D019013:CD40 Antigens / Q000096:biosynthesis; D002452:Cell Count; D003521:Cyclopropanes / Q000008:administration & dosage / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D020405:Dermis / Q000166:cytology / Q000276:immunology / Q000473:pathology; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007114:Immunization; D007271:Injections, Intradermal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007509:Irritants / Q000008:administration & dosage / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000473:pathology
chemical_list: D015415:Biomarkers; D019013:CD40 Antigens; D003521:Cyclopropanes; D004137:Dinitrochlorobenzene; D006684:HLA-DR Antigens; D007509:Irritants; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C029402:diphenylcyclopropenone