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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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Flux of blood cells and serum cytokines in PFAPA. Proposed oscillations in the abundance of blood cell populations and inflammatory cytokines over time (x-axis: h, hours; d, days; wk, weeks) in a typical PFAPA cycle. Pro-inflammatory cytokines in the serum (TNFα, IL1β, IFNγ, IL6) appear early after the onset of fever [22] and are maintained (IL6) or rapidly decline (TNFα, IL1β, IFNγ) as IFNγ-induced chemokines (MIG, IP10) appear. Lymphocyte activators IL7 and IL17 may be constitutively suppressed. The febrile period is associated with increased neutrophils (PMN) and monocytes (Mo) as well as decreased lymphocytes (Lym). Eosinophils (Eos) are in sparse abundance in both febrile and afebrile intervals while thrombocytes (Thr) rise specifically in the afebrile period. * indicates the onset of fever.
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Figure 5: Flux of blood cells and serum cytokines in PFAPA. Proposed oscillations in the abundance of blood cell populations and inflammatory cytokines over time (x-axis: h, hours; d, days; wk, weeks) in a typical PFAPA cycle. Pro-inflammatory cytokines in the serum (TNFα, IL1β, IFNγ, IL6) appear early after the onset of fever [22] and are maintained (IL6) or rapidly decline (TNFα, IL1β, IFNγ) as IFNγ-induced chemokines (MIG, IP10) appear. Lymphocyte activators IL7 and IL17 may be constitutively suppressed. The febrile period is associated with increased neutrophils (PMN) and monocytes (Mo) as well as decreased lymphocytes (Lym). Eosinophils (Eos) are in sparse abundance in both febrile and afebrile intervals while thrombocytes (Thr) rise specifically in the afebrile period. * indicates the onset of fever.

Mentions: Herein we report oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome. An increase in circulating monocytes and thrombocytes and a major decline in circulating eosinophils are novel findings. Further, we find a relatively modest level of pro-inflammatory cytokines in the sera ~15 hours after the onset of fever with a tendency towards an IFNγ-driven inflammatory response and suppressed levels of T cell-associated cytokines during the afebrile interval. Cytokine and blood cell oscillations in PFAPA syndrome are illustrated Figure 5. Future investigations are required to conclusively discern which cells and cytokines are associated with inflammation (fever) in general and which are specific to febrile episodes in PFAPA syndrome. Advances of this nature at the cellular and molecular level will facilitate the identification of biomarkers of disease or players in disease pathogenesis.


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)

Flux of blood cells and serum cytokines in PFAPA. Proposed oscillations in the abundance of blood cell populations and inflammatory cytokines over time (x-axis: h, hours; d, days; wk, weeks) in a typical PFAPA cycle. Pro-inflammatory cytokines in the serum (TNFα, IL1β, IFNγ, IL6) appear early after the onset of fever [22] and are maintained (IL6) or rapidly decline (TNFα, IL1β, IFNγ) as IFNγ-induced chemokines (MIG, IP10) appear. Lymphocyte activators IL7 and IL17 may be constitutively suppressed. The febrile period is associated with increased neutrophils (PMN) and monocytes (Mo) as well as decreased lymphocytes (Lym). Eosinophils (Eos) are in sparse abundance in both febrile and afebrile intervals while thrombocytes (Thr) rise specifically in the afebrile period. * indicates the onset of fever.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Flux of blood cells and serum cytokines in PFAPA. Proposed oscillations in the abundance of blood cell populations and inflammatory cytokines over time (x-axis: h, hours; d, days; wk, weeks) in a typical PFAPA cycle. Pro-inflammatory cytokines in the serum (TNFα, IL1β, IFNγ, IL6) appear early after the onset of fever [22] and are maintained (IL6) or rapidly decline (TNFα, IL1β, IFNγ) as IFNγ-induced chemokines (MIG, IP10) appear. Lymphocyte activators IL7 and IL17 may be constitutively suppressed. The febrile period is associated with increased neutrophils (PMN) and monocytes (Mo) as well as decreased lymphocytes (Lym). Eosinophils (Eos) are in sparse abundance in both febrile and afebrile intervals while thrombocytes (Thr) rise specifically in the afebrile period. * indicates the onset of fever.
Mentions: Herein we report oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome. An increase in circulating monocytes and thrombocytes and a major decline in circulating eosinophils are novel findings. Further, we find a relatively modest level of pro-inflammatory cytokines in the sera ~15 hours after the onset of fever with a tendency towards an IFNγ-driven inflammatory response and suppressed levels of T cell-associated cytokines during the afebrile interval. Cytokine and blood cell oscillations in PFAPA syndrome are illustrated Figure 5. Future investigations are required to conclusively discern which cells and cytokines are associated with inflammation (fever) in general and which are specific to febrile episodes in PFAPA syndrome. Advances of this nature at the cellular and molecular level will facilitate the identification of biomarkers of disease or players in disease pathogenesis.

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