Immunology Letters 95 (2004) 37–44 Absence of interleukin-3 does not affect the severity of local and systemic anaphylaxis but does enhance eosinophil infiltration in a mouse model of allergic peritonitis Nicole F. Neel, Blaine M. Creasy, Jennifer N. Rankin, Elizabeth M. Pierce, Margaret E. McCoy, Rebecca H. Daner, Jessica A. Fowler, Janet C. Daniel, Chris S. Lantz ∗ Department of Biology, James Madison University, Harrisonburg, VA 22807, USA Received 21 March 2004; received in revised form 3 June 2004; accepted 8 June 2004 Available online 14 July 2004 Abstract Interleukin-3 (IL-3), which is derived from T cells and other sources, can promote the differentiation, proliferation, and migration of mast cells, basophils, and eosinophils. However, little is known about the ability of IL-3 to regulate the function of these cells in IgE-dependent and -independent allergic responses in vivo. Therefore, we sought to investigate the extent to which endogenously produced IL-3 can influence mast cell secretory function, the expression of local and systemic anaphylactic responses, and ragweed-induced eosinophilic peritonitis. We found that peritoneal mast cells from IL-3 deficient (IL-3 -/-) mice released less serotonin following challenge with low doses of anti-IgE antibody or antigen ex vivo than do cells isolated from corresponding wild-type (IL-3 +/+) mice. Both IL-3 -/- and +/+ mice expressed equivalent IgE-dependent passive cutaneous anaphylaxis responses following challenge with specific antigen and exhibited equivalent active systemic anaphylaxis responses to ovalbumin as assessed by changes in body temperature, death rates, total IgE production, and histamine release. In contrast, ragweed allergen immunization and peritoneal allergen challenge resulted in eosinophil recruitment that was greater in IL-3 -/- mice than in IL-3 +/+ mice. Our data demonstrates that IL-3 does not appear to be essential for local or systemic anaphylaxis. However, IL-3 production in vivo was found to enhance the mediator release from freshly isolated peritoneal mast cells stimulated ex vivo, and, unexpectedly, to inhibit the accumulation of eosinophils associated with a ragweed-induced allergic peritonitis model. © 2004 Elsevier B.V. All rights reserved. Keywords: Allergy; Anaphylaxis; Eosinophil; Hypersensitivity; Interleukin-3; Mast cell; Peritonitis; Ragweed 1. Introduction The cytokine interleukin-3 (IL-3), which can be derived from T cells and other sources, is well documented at pro- moting the in vitro differentiation and proliferation of murine hematopoietic progenitor cells, leading to the generation of basophils, neutrophils, macrophages, eosinophils, basophils, erythrocytes, megakaryocytes, and dendritic cells [1–4]. Ad- ministration of IL-3 to mice [5,6], experimental primates [7], and humans [1] can promote hematopoiesis in vivo as well. In both humans and mice, stem cell factor (SCF, also known as KIT ligand) is a crucial mast cell developmental, survival, and proliferation factor [8–10]. Likewise, IL-3 is known to ∗ Corresponding author. Tel.: +1-540-568-2840; fax: +1-540-568-3333. E-mail address: lantz2cs@jmu.edu (C.S. Lantz). be a major growth and differentiation factor for rodent mast cells whereas data are less clear for human mast cells [8–10]. In humans, the ability of IL-3 to promote mast cell devel- opment appears to be restricted to certain mast cell subpop- ulations and the extent to which they express receptors for IL-3 [11–14]. In addition to its effects on the development of mast cells, basophils, and other hematopoietic cells, IL-3 can also enhance antigen presentation for T cell-dependent responses, augment macrophage cytotoxicity and adhesion, promote the secretory function of eosinophils and basophils, and participate in inflammation by inducing expression of adhesion molecules on human endothelial cells [15–22]. Despite these numerous activities, mice lacking IL-3 by homologous recombination in embryonic stem cells display intact steady-state hematopoiesis [23–25] and have normal numbers of tissue mast cells [26]. These findings suggest that IL-3 is either not involved in hematopoietic cell development 0165-2478/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.imlet.2004.06.002