Bestimmung von intrazellulären und zirkulierenden Zytokinen im Fieberschub und im fieberfreien Intervall bei 14 Kindern mit vier der häufigsten autoinflammatorischen Fiebersyndromen

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-gamma serum concentrations compared to
symptom-free periods and to controls, with IL-1beta, TNF-alpha and
IL-12p70 levels being significantly higher than in controls.
Lymphocytic IFN-gamma and CD8+ IL-2 production was consistently
significantly elevated compared to healthy children. During the
asymptomatic period, serum concentrations of IL-1beta, IL-6,
TNF-alpha and IL-12p70 were significantly increased compared to
controls. Intracellular TNF-alpha 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.