title: Cytokine expression patterns associated with systemic adverse events following smallpox immunization.
abstract: Vaccinia virus is reactogenic in a significant number of vaccinees, with the most common adverse events being fever, lymphadenopathy, and rash. Although the inoculation is given in the skin, these adverse events suggest a robust systemic inflammatory response. To elucidate the cytokine response signature of systemic adverse events, we used a protein microarray technique to precisely quantitate 108 serum cytokines and chemokines in vaccine recipients before and 1 week after primary immunization with Aventis Pasteur smallpox vaccine. We studied 74 individuals after vaccination, of whom 22 experienced a systemic adverse event and 52 did not. The soluble factors most associated with adverse events were selected on the basis of voting among a committee of machine-learning methods and statistical procedures, and the selected cytokines were used to build a final decision-tree model. On the basis of changes in protein expression, we identified 6 cytokines that accurately discriminate between individuals on the basis of adverse event status: granulocyte colony-stimulating factor, stem cell factor, monokine induced by interferon-gamma (CXCL9), intercellular adhesion molecule-1, eotaxin, and tissue inhibitor of metalloproteinases-2. This cytokine signature is characteristic of particular inflammatory response pathways and suggests that the secretion of cytokines by fibroblasts plays a central role in systemic adverse events.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: McKinney
authors.forename: David M
authors.initials: DM
authors.lastname: Reif
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rock
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edwards
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kingsmore
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000293:Adolescent; D000328:Adult; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D003663:Decision Trees; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000276:immunology; D008297:Male; D012872:Skin Diseases, Vesiculobullous / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D012899:Smallpox / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000009:adverse effects*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D012900:Smallpox Vaccine; D018799:Intercellular Adhesion Molecule-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D016179:Granulocyte Colony-Stimulating Factor