IL‐33/ST2 signalling contributes to carrageenin‐induced innate inflammation and inflammatory pain: role of cytokines, endothelin‐1 and prostaglandin E2

• DOI: 10.1111/bph.12110
• Publication Date: 2013-01-24T18:35:08Z
• Authors: AC Zarpelon; TM Cunha; JC Alves‐Filho; LG Pinto; SH Ferreira; IB McInnes; D Xu; FY Liew; FQ Cunha; WA Verri
• Keywords: Inflammation; Male; Mice, Knockout; Mice, Inbred BALB C; 0303 health sciences; Dose-Response Relationship, Drug; Endothelin-1; Interleukins; Pain; Receptors, Interleukin; Carrageenan; Interleukin-33; Interleukin-1 Receptor-Like 1 Protein; Dinoprostone; Disease Models, Animal; Mice; 03 medical and health sciences; Animals; Cytokines; Female; RNA, Messenger; Inflammation Mediators

IL-33 signals through ST2 receptors and induces adaptive innate inflammation. IL-33/ST2 is involved in inflammation-induced pain. Here, we have investigated the contribution of IL-33/ST2-triggered mechanisms to carrageenin-induced inflammation.Carrageenin- IL-33-induced inflammatory responses were assessed BALB/c- (WT) ST2-deficient ((-/-) ) mice as follows: oedema (plethysmometer), myeloperoxidase activity (colorimetric assay), mechanical hyperalgesia (electronic version von Frey filaments), cytokine levels (ELISA), PGE2 (RIA), mRNA expression (quantitative PCR), drug treatments targeting leukocyte recruitment (fucoidin), TNF-α (infliximab), CXCL1 (antibody CXCL1), IL-1 (IL-1ra), endothelin ETA (clazosentan) ETB (BQ788) COX (indomethacin).Carrageenin injection increased production paw skin samples. Carrageenin-induced oedema, reduced ST2(-/-) compared with WT mice, effects mimicked by paw. Furthermore, was fucoidin suggesting a role for recruited leukocytes its hyperalgesic effect. naïve TNF, CXCL1, IL-1, while ST2-dependent TNF-α, IL-1β, IL-10 preproET-1 expression. Combining carrageenin at doses that ineffective single treatment induced significant hyperalgesia, manner.IL-33/ST2 signalling triggers mediators contributing These data reinforces importance target inflammation