Neutrophil Activation in Patients with ASA-Induced Urticaria Sung-Jin Choi & Young-Min Ye & Gyu-Young Hur & Seung-Youp Shin & Jae-Ho Han & Hae-Sim Park Received: 19 November 2007 / Accepted: 14 December 2007 # Springer Science + Business Media, LLC 2007 Abstract The pathogenic mechanism of acetyl salicylic acid (ASA)-induced urticaria (AIU) is not fully understood. We compared the levels of neutrophil activation and related cytokines in patients with ASA-intolerant acute urticaria (AIAU) and ASA-intolerant chronic urticaria (AICU). A total of 51 patients with AIAU, 88 patients with AICU, and 102 normal controls (NC) were enrolled in this study. The serum levels of myeloperoxidase (MPO), interleukin-8 (IL-8), and IL-18 were compared among the three groups. The serum levels of MPO were highest in the AIAU group, followed by the AICU and NC groups, and the serum levels of IL-18 were significantly higher in the AIAU and AICU groups than in NC group. Within the AIU groups, significant correlations were noted between the levels of MPO and IL-8, and IL-8 and IL-18. In conclusion, neutrophil activation, which was associated with the levels of IL-8 and IL-18 in the AIAU group, may be involved in the pathogenic mechanism of AIU. A role for IL-18 in the pathogenesis of AIU is also suggested. Keywords ASA-intolerant acute urticaria . IL-8 . IL-18 . neutrophil activation Introduction The clinical features of aspirin (acetyl salicylic acid [ASA]) hypersensitivity include aspirin-intolerant asthma (AIA), aspirin-intolerant acute or chronic urticaria/angioedema (AIAU or AICU, respectively), anaphylaxis, and rarely hypersensitivity pneumonitis [1, 2]. Among these conditions, AIA and aspirin-intolerant urticaria/angioedema (AIU) are the most prevalent. Chronic urticaria is defined as daily or almost daily symptoms lasting for more than 6 weeks [3]. There is general agreement that aspirin aggravates chronic urticaria in 20–40% of patients [4], who are classified as AICU. Patients whose cutaneous symptoms improve within 6 weeks are classified as AIAU [3]. The pathogenesis of AIA is known to involve the inhibition of cyclooxygenase by ASA or other nonsteroidal anti-inflammatory drugs, resulting in enhanced production of leukotrienes (LTs), which are potent inflammatory mediators synthesized from arachidonic acid via a sequential pathway [1, 2, 5]. However, knowledge of the pathogenic mechanism of AIU is limited, as there are no published data comparing the clinical features and pathogenic mechanisms of AIAU and AICU. One major feature of urticaria is the release of histamine from activated mast cells, which leads to raised, superficial, erythematous wheals and intense pruritus [3]. Neutrophilic urticaria, a subtype of urticaria characterized by neutrophil- ic extravasation and a predominantly neutrophilic dermal infiltrate [6–8], has been observed in cases of chronic, cholinergic, and cold urticaria [9, 10]. However, no published data have demonstrated neutrophil involvement in AIU. Myeloperoxidase (MPO) is a marker of neutrophil activation in serum, and the cytokine interleukin-8 (IL-8) causes neutrophil chemotaxis in vitro [11]. Recent data have indicated a role for the cytokine IL-18 in the J Clin Immunol DOI 10.1007/s10875-007-9165-0 S.-J. Choi : Y.-M. Ye : G.-Y. Hur : H.-S. Park (*) Department of Allergy and Rheumatology, Ajou University School of Medicine, San-5, Wonchondong, Youngtonggu, Suwon, Korea e-mail: hspark@ajou.ac.kr S.-Y. Shin Department of Otolaryngology, Kyunghee University School of Medicine, Seoul, Korea J.-H. Han Department of Pathology, Ajou University School of Medicine, Suwon, Korea