Open Access

ARTICLE

Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response

Silvia Stojanov^1,*, Florian Hoffmann^1,*, Anja Kéry¹, Ellen D. Renner^1,2, Dominik Hartl¹, Peter Lohse³, Kristina Huss¹, Peter Fraunberger³, James D. Malley⁴, Stephanie Zellerer¹, Michael H. Albert¹, Bernd H. Belohradsky¹

1 Department of Infectious Diseases and Immunology, Children’s Hospital, University of Munich, Germany
2 Department of Pediatrics, University of Washington & Children’s Hospital, Seattle, USA
3 Department of Clinical Chemistry - Grosshadern, University of Munich, Germany
4 Center for Information Technology, National Institutes of Health, Bethesda, USA

European Cytokine Network 2006, 17(2), 90-97.

Accepted 08 March 2006;

Abstract

PFAPA syndrome is characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis, and/or cervical adenitis. It is of unknown etiology and manifests usually before 5 years of age. We determined serum and intracellular cytokine levels in six PFAPA patients (4 males, 2 females, mean age 8 years (± 1.2 SEM), range 4-13) during the symptom-free period as well as 6-12 hours and 18-24 hours after fever onset. Values were compared to age-matched, healthy controls. Febrile PFAPA attacks led to a significant increase in IL-6 and IFN-γ serum concentrations compared to symptom-free periods and to controls, with IL-1β, TNF-α and IL-12p70 levels being significantly higher than in controls. Lymphocytic IFN-γ and CD8+ IL-2 production was consistently significantly elevated compared to healthy children. During the asymptomatic period, serum concentrations of IL-1β, IL-6, TNF-α and IL-12p70 were significantly increased compared to controls. Intracellular TNF-a synthesis was not elevated at any time point. Soluble TNFRp55 levels were even lower in between febrile episodes, reaching values comparable to controls during attacks, whereas soluble TNFRp75 levels increased during attacks compared to healthy children. Anti-inflammatory IL-4 in serum was at all times lower in PFAPA patients compared to controls with no difference in levels of intracellular IL-4 and IL-10 or serum IL-10. The observed increase of pro-inflammatory mediators, even between febrile attacks, suggests a dysregu-lation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.

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Keywords

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