Carry-over effect on IFN-gamma production induced by allergen-specific immunotherapy Giorgio Ciprandi a, ⁎, Maria Pia Sormani b , Gilberto Filaci a , Daniela Fenoglio a a Department of Internal Medicine-CEBR, University of Genoa, Genoa, Italy b Department of Health Sciences, Unit of Biostatistics, University of Genoa, Genoa, Italy abstract article info Article history: Received 7 April 2008 Received in revised form 16 June 2008 Accepted 11 July 2008 Keywords: Allergic rhinitis Pollens Mites Th1 cells IFN-γ production ELISPOT Background: Allergic rhinitis is characterized by Th2 polarization and defective IFN-γ production. Specific immunotherapy determines an allergen-specific clinical improvement. Aim of the study: It was to evaluate whether a course of pre-seasonal SLIT with pollen allergen extract might affect the in vitro IFN-γ production using Dermatophagoides farinae (Df) allergen as stimulus, in patients presenting with rhinitis due to pollen allergy. Methods: Thirty-nine AR patients with pollen allergy were included in the study. They assumed pre-seasonal SLIT for 3 months. IFN-γ-specific producing cells were assessed by cytokine ELISPOT before and 3 months after the SLIT course end. Results: SLIT provided a significant increase of both pollen-induced and Df-induced IFN-gamma production (p b 0.001). Conclusions: The present study provides evidence that though the defective IFN-γ production is allergen- specific in allergic subjects, the SLIT increasing effects on IFN-γ may be non-specific. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Allergic rhinitis (AR) is sustained by a mucosal inflammation orchestrated by T helper2 (Th2) cells [1]. In addition, peripheral blood mononuclear cells (PBMC) of AR patients display a predominant interleukin-4 (IL-4) production by Th2 cells over interferon-gamma (IFN-γ) expression by Th1 cells, which constitutes the so-called “Th2 polarization” [2]. This Th2 polarization is typically characterized by a reduced IFN-γ production. Moreover, the therapeutic administration of subcutaneous increas- ing doses of the causal allergen, such as the specific immunotherapy (SIT), reduces allergic symptoms and the need for medications in patients with AR and mild forms of asthma, as stated in a World Health Organization position paper [3]. The SIT effectiveness depends on achieving clinical tolerance towards the causal allergen. Even though the exact mechanism of action of SIT is not completely understood, there is evidence that it induces hyposensitization by modifying peripheral and mucosal predominant Th2-responses into a prevalent Th1-polarization, as evidenced by an increased production of IFN-γ [4,5]. This issue reinforces the concept concerning the functional dichotomy between Th1 and Th2 response. Recently, sublingual immunotherapy (SLIT) has been developed and introduced to minimize possible serious adverse events as it is very safe and effective. About the SLIT mechanisms of action on immune response, two studies have demonstrated that also SLIT was able to increase allergen-specific-driven IFN-γ production [6,7], another one showed that SLIT may also prevent the onset of new sensitisations [8]. Moreover, it is well known that the clinical effects of SIT are actually allergen-specific [8]. However, all published studies investigated the IFN-γ production induced only by the causal allergen. Therefore, the aim of the present study was to evaluate whether a course of pre- seasonal SLIT with pollen allergen extract might affect in vitro IFN-γ production induced by a non-causal allergen, such as Dermatopha- goides farinae, in patients monosensitized to pollens. 2. Materials and methods Thirty-nine AR patients with pollen allergy (17 females and 22 males, mean age 37.5 years, range 14–75) were included in the study. All of them were monosensitized to pollen: 16 to Betula alba, 16 to Parietaria, and 7 to Graminaceae. The relevant causality of the pollen was demonstrated by a positive allergen-specific conjunctival chal- lenge. Mite allergy was excluded both by a negative skin prick test and negative history for perennial symptoms. Patients suffered from seasonal allergic rhinitis alone and with moderate nasal symptoms during the previous pollen seasons. The study was conducted with the International Immunopharmacology 8 (2008) 1622–1625 ⁎ Corresponding author. Ospedale San Martino, Largo R. Benzi 10,16132 Genoa, Italy. Tel.: +00 39 10 35338120; fax: +00 39 10 3537573. E-mail address: gio.cip@libero.it (G. Ciprandi). 1567-5769/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.intimp.2008.07.007 Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp