TY - JOUR
T1 - Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response
AU - Stojanov, Silvia
AU - Hoffmann, Florian
AU - Kéry, Anja
AU - Renner, Ellen D.
AU - Hartl, Dominik
AU - Lohse, Peter
AU - Huss, Kristina
AU - Fraunberger, Peter
AU - Malley, James D.
AU - Zellerer, Stephanie
AU - Albert, Michael H.
AU - Belohradsky, Bernd H.
PY - 2006
Y1 - 2006
N2 - 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 IIL-12p70 were significantly increased compared to controls. Intracellular TNF-α 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 dysregulation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.
AB - 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 IIL-12p70 were significantly increased compared to controls. Intracellular TNF-α 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 dysregulation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.
KW - Cytokine
KW - IFN-γ
KW - IL-Iβ
KW - Inflammation
KW - PFAPA syndrome
KW - Periodic fever
UR - http://www.scopus.com/inward/record.url?scp=33747468990&partnerID=8YFLogxK
M3 - Article
C2 - 16840027
AN - SCOPUS:33747468990
SN - 1148-5493
VL - 17
SP - 90
EP - 97
JO - European Cytokine Network
JF - European Cytokine Network
IS - 2
ER -