Periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy syndrome is associated with activation of GM-CSF and burst-like expression of IL-8 in peripheral blood.

INTRODUCTION: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy (PFAPA) is an autoinflammatory syndrome characterized by periodic fever with aphthous stomatitis, cervical lymphadenopathy, myalgia, and abdominal pain. Peripheral blood concentrations of selected cytokines of PFAPA patients during and between febrile episodes were analyzed in a search for PFAPA-specific molecular signature. METHODS: 23 children with PFAPA (age 6.07 +/- 2.94 years, range 5-9 years) and three control children with severe oropharyngeal infections (age 6.2 +/- 7.95 years, range 1-17 years) participated in the study. Peripheral blood concentrations of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, GM-CSF, TNF-alpha were measured using Luminex technology. RESULTS: PFAPA febrile episodes were characterized by detection of GM-CSF - 134.07 +/- 315.5 pg/mL; significant (P < 0.001), compared to baseline and controls, elevation of concentrations of IL-8 (3193.7 +/- 2508 pg/mL vs. 100.36 +/- 119. pg/mL vs. 2.04 +/- 4.08 pg/mL, respectively), IL-6 (1355.38 +/- 2026.53 pg/mL vs. 28.8 +/- 44.2 pg/mL and 27.13 +/- 26.42 pg/mL, respectively). IL-1beta was detected only in febrile and afebrile PFAPA patients (922.8 +/- 1639 pg/mL vs. 10.98 +/- 19.4 pg/ml, P < 0.002, respectively), but not in controls. Peripheral blood concentration of TNFalpha did not differ significantly between study groups. IL-2, IL-4, IL-5, and IL-10 were negligible in all study subjects. DISCUSSION: PFAPA febrile episodes are characterized by activation of GM-CSF and IL-8 with Th1 skewing. We propose a molecular mechanism governing this phenomenon.