Brief Definitive Report Different serum cytokine levels in chronic vs. acute Anisakis simplex sensitization-associated urticaria A. DASCHNER, 1 M. RODERO, 2 C. DE FRUTOS, 1 A. VALLS, 1 F. VEGA, 1 C. BLANCO 1 & C. CUÉLLAR 2 1 Servicio de Alergia, Instituto de Investigación Sanitaria – Hospital Universitario de la Princesa, Diego de León, Madrid, Spain, 2 Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense, Madrid, Spain SUMMARY The knowledge on immune mechanisms of chronic urticaria (CU) at the cytokine level is widely scarce. We compared pro- and anti-inflammatory as well as Th1- and Th2-associ- ated serum cytokine levels in two phenotypes of CU: associ- ated with (CU+) and without (CU)) sensitization against Anisakis simplex, a ubiquitous fish parasite, that has been associated with acute urticaria in gastro-allergic anisakiasis (GAA) and with CU+. Thirteen CU+ and 19 CU) patients were compared with 13 GAA patients and 15 control sub- jects forcytokines, measured by cytometric bead array. Urti- caria activity score was positively correlated with IL-6 in CU). Serum levels of IL-10 were lower in CU+ and CU) with respect to the control group. Median IFN-c was lower in all urticaria groups. Patients with previous parasit- ism by A. simplex displayed higher TGF-b levels than sub- jects without previous parasitism. The main finding was lower levels of IL-17 in CU+ with respect to GAA or con- trols, with a further tendency to even lower levels in CU). Different urticaria phenotypes are associated with distinct serum cytokine levels. Keywords allergy, Anisakis simplex, cytokine, flow cytome- try, human Abbreviations: CU, chronic urticaria; CU+, Anisakis sim- plex sensitization-associated chronic urticaria; CU), chronic urticaria without sensitization against Anisakis simplex; GAA, gastro-allergic anisakiasis INTRODUCTION Chronic urticaria (CU) is a frequent and disabling illness occurring worldwide in 0Æ1% of the population and has repeatedly been shown to affect quality of life (1). While CU induced by infectious agents has been proposed over the last 30 years, publications describing these associations are anecdotic (2). Whereas CU is not a typical feature of allergic disease, it is frequently assessed in a clinical allergological setting. Acute urticaria of the immediate-type reaction is frequently IgE-mediated, but CU is only rarely associated with an IgE- mediated immunologic feature. Otherwise, one frequent phenotype of CU in our area (Central Spain) is its associa- tion with sensitization against the ubiquitous fish parasite Anisakis simplex (3). In our area, this phenotype of patients with CU constitutes up to 50% of patients attended for allergological evaluation, and in a relevant subgroup of these patients, sensitization against A. simplex was explained by a previous parasitism episode by A. simplex (4). Gastro-allergic anisakiasis (GAA) is a well-established clinical entity, where acute short-lived, IgE-mediated urti- caria, angio-oedema or anaphylaxis accompanies acute A. simplex infection (5,6). It has been shown that the immu- nologic response accompanying this short-lived parasitism is accompanied by an important polyclonal stimulation of different isotypes of immunoglobulins comprising a mixed Th1- and Th2-mediated reaction (7). Otherwise, the possible immunologic mechanisms in A. simplex sensitization-asso- ciated CU (from now on CU+) are not clearly established. Previous studies did not establish CU to be associated with a polarized Th1 or Th2 milieu but demonstrated a mainly Th0 or mixed Th1 ⁄ Th2 profile (8). Our hypothesis was that CU could be associated with the Th17 or regula- tory, rather than the Th1 ⁄ Th2, axis. Further, in the model of A. simplex sensitization-associated urticaria, the pheno- type of urticaria (acute vs. chronic) could be attributed to Correspondence: Dr Alvaro Daschner, Servicio de Alergia, Hospital Universitario de la Princesa, C ⁄ Diego de León, 62, E-28006 – Madrid, Spain (e-mail: alvarodaschner@gmail.com). Disclosures: None. Received: 28 December 2010 Accepted for publication: 31 January 2011 Parasite Immunology, 2011, 33, 357–362 DOI: 10.1111/j.1365-3024.2011.01282.x Ó 2011 Blackwell Publishing Ltd 357