Cytokine expression patterns associated with systemic adverse events following smallpox immunization.

McKinney BA, Reif DM, Rock MT, Edwards KM, Kingsmore SF, Moore JH, Crowe JE
J Infect Dis. 2006 194 (4): 444-53

PMID: 16845627 · PMCID: PMC1620015 · DOI:10.1086/505503

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.

MeSH Terms (16)

Adolescent Adult Chemokine CCL11 Chemokines, CC Cytokines Decision Trees Female Granulocyte Colony-Stimulating Factor Humans Intercellular Adhesion Molecule-1 Male Skin Diseases, Vesiculobullous Smallpox Smallpox Vaccine Tissue Inhibitor of Metalloproteinase-2 Vaccinia virus

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