ORIGINAL ARTICLE Evaluation of the correlation between tissue reaction and cytokines patterns induced by Alternaria alternate in mice Zahra Moosavi & Ali Reza Khosravi & Farhang Sasani & Mohammad Javad Gharagozloo & Hojjatollah Shokri & Zahra Tootian Received: 26 April 2009 / Accepted: 20 October 2009 / Published online: 12 November 2009 # Springer-Verlag London Limited 2009 Abstract Alternaria alternata is well-known as a source of allergenic components in the cell wall and cytoplasm of conidia and hyphae that cause respiratory allergic disorders. The purpose of this study was to evaluate tissue reaction and Th 2 cytokines in mice exposed to A. alternata. A. alternata was cultured, and fungal extract was prepared by freeze–defreeze and sonication methods. BALB/c mice in one group were sensitized by two intraperitoneal injections of A. alternata extract and then intra-nasally challenged with spores suspended in sterile normal saline solution, and in another group, mice only received spores intra-nasally. Blood sampling and necropsy were performed at 1 and 72 h after spore inhalation. Histopathology demonstrated an inflammatory response with cells including lymphocytes, macrophages, neutrophils and eosinophils present and mucus hypersecretion in the lungs and airway epithelial cell hyperplasia and necrosis observed in sensitized and non-sensitized mice. Sera were analyzed by ELISA to determine serum levels of Interleukin (IL)-4 and IL-13 in immediate response and late-phase reaction, respectively. Increasing Th 2 cytokine (IL-4 and IL-13) levels in the sera was also observed in the sensitized and challenged mice. The results showed that exposure to extract and then spores of A. alternata induced rapid and highly elevated production of IL-4 and IL-3. These cytokines were associated with respiratory histopathological changes. Keywords Alternaria alternate . IL-4 . IL-13 . Lung . Macrophage Introduction Alternaria species are common indoor and outdoor air-borne fungi, which have been identified as causative agents of respiratory allergic disorders in humans and domestic animals (Downs et al. 2001; Dye et al. 2005). Alternaria produces many different proteins that function as allergens (Sanchez and Bush 2001). Immediate (type 1) hypersensitivity results from the activation of the Th 2 subset of CD4+ helper T cells by environmental antigens, leading to the production of IgE antibodies, which become attached to mast cells. When these IgE molecules bind the antigen (allergen), the mast cells are triggered to release mediators that transiently affect vascular permeability and induce smooth muscle contraction in various organs and may stimulate more prolonged inflammation (the late- phase reaction). When individuals who were sensitized by previous exposure to an allergen are re-exposed, the allergen binds to multiple specific IgE molecules on mast cells, usually at or near the site of allergen entry (Kumar et al. 2007). Often, the IgE-triggered reaction has two well- Z. Moosavi : F. Sasani : M. Javad Gharagozloo Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran A. R. Khosravi (*) : H. Shokri Mycology Research Center, Faculty of Veterinary Medicine, University of Tehran, P.O. Box 14155-6453, Tehran, Iran e-mail: Khosravi@ut.ac.ir Z. Tootian Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Comp Clin Pathol (2010) 19:607–610 DOI 10.1007/s00580-009-0931-7