We did not include an access food challenge and were therefore unable to determine individual changes in reaction threshold. than the placebo group (median 1710 mg vs. 85 mg, p=0.011). Mechanistic studies demonstrated a decrease in prick pores and skin test wheal size (p=0.020) and decreased basophil responsiveness after activation with 10?2 mcg/ml (p=0.009) and 10?3 mcg/ml (p=0.009) of peanut. Peanut-specific IgE improved over the initial 4 weeks (p=0.002) Nalbuphine Hydrochloride then steadily decreased over the remaining 8 weeks (p=0.003) while peanut-specific IgG4 increased during the 12 months (p=0.014). Lastly, IL-5 levels decreased after 12 months (p=0.015). No statistically significant changes were found in IL-13 levels, the percent of T regulatory cells, or IL-10 and IFN-gamma production. Summary Peanut sublingual immunotherapy is able to safely induce medical desensitization in peanut allergic children with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine if continued peanut sublingual immunotherapy is able to induce long-term immune tolerance. strong class=”kwd-title” Keywords: peanut allergy, sublingual immunotherapy, Eptifibatide Acetate desensitization, food allergy INTRODUCTION Food allergy continues to be a significant public health problem in industrialized countries. The National Center for Health Statistics estimated that approximately 3.9% of US children in 2007 reported a food allergy in the past 12 months. This included an 18% increase in prevalence from 1997-2007.1 Of all the foods implicated, peanut remains one of the most common and is considered one of the most severe with the majority of food related life threatening and fatal allergic reactions due to peanut ingestion.2, 3 Of the more than 3 million Americans with a peanut or tree nut allergy4, fewer than 20% will outgrow the allergy naturally.5, 6 The current standard of care remains strict avoidance and the treatment of accidental ingestions with intramuscular epinephrine and/or antihistamines. A significant amount of research has focused on the use of immunotherapy for the treatment of food allergy. Although subcutaneous immunotherapy (SCIT) has been successfully used in the treatment of allergic rhinitis and asthma for many years, early attempts with SCIT for food allergy resulted in an unacceptably high rate of systemic reactions.7 In the past few years, several different types of therapy for food allergy have been studied including oral immunotherapy (OIT), which involves ingesting milligrams to grams of allergen in the form of flour combined in a food vehicle. Ongoing research with OIT has shown interesting results but this type of therapy needs much more study.8-11 In contrast, sublingual immunotherapy (SLIT) involves the administration of small amounts (micrograms to milligrams) of allergen extract under the tongue. Although its use has been limited in the United States, SLIT has been used commonly in Europe as an alternative to SCIT for allergic rhinitis. It offers a novel means of treatment for food allergy and seems well suited for several reasons. First, oral Langerhans cells that take up antigen within the mouth have been shown to have tolerogenic properties, potentially accounting for the efficacy of aeroallergen SLIT.12 Second, SLIT is easily administered especially when compared to receiving injections, such as with SCIT, or ingesting large amounts of food, as with OIT. Finally, systemic reactions have been uncommon13, which may be secondary to the relatively small doses used to achieve clinical efficacy. We present the first study on the use of SLIT in the treatment of peanut allergy in children. The goal of our double-blinded, placebo-controlled study was to evaluate the safety and efficacy of peanut SLIT after 12 months of therapy. In addition, we investigated whether any increase in reaction threshold would be accompanied by immunologic changes indicative of a significant change in the Nalbuphine Hydrochloride allergic response. METHODS Study Design The primary outcome of the study was to evaluate the reaction threshold to peanut ingestion after 12 months of peanut SLIT therapy compared to placebo. Food challenges to assess the primary endpoint were scheduled after 12 and 18 months of SLIT therapy. A planned interim analysis was performed after 18 months of enrollment to evaluate the primary endpoint and whether food challenges at later time points would be necessary to further assess the primary endpoint. Secondary endpoints included the frequency and severity of side effects to dosing as well as changes in several immunological parameters, including peanut-specific IgE and IgG4, basophil activation, skin test reactivity, the cytokines IL-5, IL-13, IL-10 and IFN-gamma, and T regulatory cells (TRegs). Subject Recruitment Subjects age 1 to 11 years were recruited from the Duke University Medical Center Allergy and Immunology clinics and local referring physician offices. Subjects with a physician documented clinical Nalbuphine Hydrochloride history of.