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Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome.

Brown KL, Wekell P, Osla V, Sundqvist M, Sävman K, Fasth A, Karlsson A, Berg S - BMC Pediatr (2010)

Bottom Line: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval.IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. kelly.brown@gu.se

ABSTRACT

Background: This study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease.

Methods: A cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA.

Results: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.

Conclusions: Identification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

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Related in: MedlinePlus

Classic pro-inflammatory cytokines. The concentrations (pg/ml) of prototypic pro-inflammatory cytokines TNFα (left), IL1β (centre) and IL6 (right) in sera from controls (n = 3), afebrile patients (n = 3) and febrile patients ~15 hours after the onset of fever (n = 3) were measured using a multiplex bead ELISA. The lower limits for detection of IL1β and IL6 are indicated by a dotted line. Measured quantities are reported in Additional File 4, Table S3.
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Figure 3: Classic pro-inflammatory cytokines. The concentrations (pg/ml) of prototypic pro-inflammatory cytokines TNFα (left), IL1β (centre) and IL6 (right) in sera from controls (n = 3), afebrile patients (n = 3) and febrile patients ~15 hours after the onset of fever (n = 3) were measured using a multiplex bead ELISA. The lower limits for detection of IL1β and IL6 are indicated by a dotted line. Measured quantities are reported in Additional File 4, Table S3.

Mentions: A multiplex bead ELISA was used to determine the concentration of classic pro-inflammatory cytokines TNFα, IL1β and IL6 in FP sera that was drawn at approximately the same time after the onset of fever (~15 hours, n = 3). IL-6 was significantly increased in FP sera compared to control sera. The levels of TNFα and IL1β in all samples approached the lower limits of detection in the multiplex assay. Nevertheless, TNFα and IL1β concentrations were similar or slightly repressed in FP sera compared to control sera (Figure 3 and Additional File 4, Table S3). Given that the expression of IL-6 is often induced by TNFα or IL1β [21] and these cytokines were found in PFAPA sera 4 hours after the onset of fever [22], we anticipate that TNFα and IL1β peak early in the fever period then quickly approach homeostatic levels. A rapid oscillation of TNFα and IL1β in vivo occurs in response to infection [23,24].


Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome.

Brown KL, Wekell P, Osla V, Sundqvist M, Sävman K, Fasth A, Karlsson A, Berg S - BMC Pediatr (2010)

Classic pro-inflammatory cytokines. The concentrations (pg/ml) of prototypic pro-inflammatory cytokines TNFα (left), IL1β (centre) and IL6 (right) in sera from controls (n = 3), afebrile patients (n = 3) and febrile patients ~15 hours after the onset of fever (n = 3) were measured using a multiplex bead ELISA. The lower limits for detection of IL1β and IL6 are indicated by a dotted line. Measured quantities are reported in Additional File 4, Table S3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2944328&req=5

Figure 3: Classic pro-inflammatory cytokines. The concentrations (pg/ml) of prototypic pro-inflammatory cytokines TNFα (left), IL1β (centre) and IL6 (right) in sera from controls (n = 3), afebrile patients (n = 3) and febrile patients ~15 hours after the onset of fever (n = 3) were measured using a multiplex bead ELISA. The lower limits for detection of IL1β and IL6 are indicated by a dotted line. Measured quantities are reported in Additional File 4, Table S3.
Mentions: A multiplex bead ELISA was used to determine the concentration of classic pro-inflammatory cytokines TNFα, IL1β and IL6 in FP sera that was drawn at approximately the same time after the onset of fever (~15 hours, n = 3). IL-6 was significantly increased in FP sera compared to control sera. The levels of TNFα and IL1β in all samples approached the lower limits of detection in the multiplex assay. Nevertheless, TNFα and IL1β concentrations were similar or slightly repressed in FP sera compared to control sera (Figure 3 and Additional File 4, Table S3). Given that the expression of IL-6 is often induced by TNFα or IL1β [21] and these cytokines were found in PFAPA sera 4 hours after the onset of fever [22], we anticipate that TNFα and IL1β peak early in the fever period then quickly approach homeostatic levels. A rapid oscillation of TNFα and IL1β in vivo occurs in response to infection [23,24].

Bottom Line: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval.IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. kelly.brown@gu.se

ABSTRACT

Background: This study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease.

Methods: A cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA.

Results: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.

Conclusions: Identification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

Show MeSH
Related in: MedlinePlus