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Systemic Cytokine Responses in Acute Food Protein-Induced Enterocolitis (FPIES)

      Rationale

      FPIES is a non-IgE, presumably T cell-mediated gastrointestinal food allergy that manifests within 2-4 hours following food ingestion with repetitive emesis, ashen-gray appearance and lethargy; 15% progress to hypotension. FPIES pathophysiology remains to be elucidated. We sought to characterize systemic cytokine responses in acute FPIES.

      Methods

      Children with suspected FPIES were challenged according to a standard protocol. Sera were obtained immediately prior and 4-6 hours following the challenge. Cytokine levels were measured with Multiplex ELISA [pg/ml], including IL-10, IP-10 (CXCL-10), TNF-alpha, IL-2, GMCSF, IFN-alpha2, IFN-gamma, IL-12P40, IL-1a, IL-1b, IL-13, IL-6, IL-8, MCP-1, MIP1alpha/beta, RANTES, VEGF.

      Results

      Serum IL-10 levels were increased in 11 children with FPIES who reacted during the challenge (median change pre-post 11.2, inter-quartile range (IQR) 7.7; 31.4) compared to 6 children with FPIES who did not react (median change pre-post -0.8 , IQR 3.8; 3.7; P=0.006). Levels of IP-10 were also increased, although to a lesser degree, in children who reacted during challenge (median change pre-post was 34.9, IQR -21.8; 88.5) compared to those who did not react (median change pre-post -55.7, IQR -62, -43.9, P= 0.014). The levels of the remaining cytokines were not significantly different pre- and post- challenge.

      Conclusions

      Children with FPIES exhibit a strong systemic response following an acute reaction characterized by a significant increase in serum IL-10 levels and to a lesser degree, IP-10, considered a more sensitive readout for IFN-gamma, IFN-alpha and TNF-alpha. Determination of the cellular sources of IL-10 and IP-10 may shed light on the pathophysiology of FPIES.