The impact of aluminium in acid‐suppressing drugs on the immune response of BALB/c mice

Brunner, Richard; Wallmann, Julia; Szalai, Krisztina; Karagiannis, Panagiotis; Kopp, Tamara; Scheiner, Otto; Jensen‐Jarolim, Erika; Pali‐Schöll, Isabella

doi:10.1111/j.1365-2222.2007.02813.x

Cited by 37 publications

(32 citation statements)

References 34 publications

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“…Thus, having a similar effect as on the human pH levels [21] we have used repeated injections of PPI in our immunization protocol. We additionally combined it with sucralfate, as aluminum-compounds are known to establish a pronounced Th2 response [24], which was recently also evidenced for sucralfate [19,25]. As both drugs were previously reported to induce a Th2 biasing effect only in combination with the respective allergen [9,11,19], we expected a profound Th2 induction by this immunization protocol.…”

Section: Discussionmentioning

confidence: 96%

“…For an additional Th2 biasing effect [19], the aluminum containing anti-acid sucralfate was added to the solution, which was fed the animals. To further address the question of dose-dependency, we have used different OVA concentrations (0.2, 0.5, 1.0, 2.5 and 5.0 mg per mouse) for the feedings.…”

Section: Ova Feeding Under Acid-suppression Induces Antigen-specific mentioning

confidence: 99%

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Dose-dependent food allergy induction against ovalbumin under acid-suppression: A murine food allergy model

et al. 2008

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Background-Animal models are essential for analyzing the allergenic potential of food proteins and for investigating mechanisms underlying food allergy. Based on previous studies revealing acid-suppression medication as risk factor for food allergy induction, we aimed to establish a mouse model mimicking the natural route of sensitization in patients.Methods-The effect of acid-suppressing medication on murine gastric pH was assessed by intragastric pH measurements after two injections of a proton pump inhibitor (PPI). To investigate dose-dependency, mice were fed different concentrations of ovalbumin (OVA; 0.2, 0.5, 1.0, 2.5 or 5.0 mg) either with or without anti-ulcer medication. Additionally, different routes of exposure (i.p. vs. oral) were compared in a second immunization experiment. Sera were screened for OVAspecific antibody titers (IgG1, IgG2a and IgE) in ELISA and RBL assay. Clinical reactivity was evaluated by measuring rectal temperature after oral challenge and by type I skin tests.Results-Two intravenous injections of PPI significantly elevated the gastric pH from 2.97 to 5.3. Only oral immunization with 0.2 mg OVA under anti-acid medication rendered elevated IgG1, IgG2a and IgE titers compared to all other concentrations. Protein feeding alone altered antibody titers only marginally. Even though also i.p. immunizations induced high levels of specific IgE, only oral immunizations under anti-acids induced anaphylactic reactions evidenced by a significant decrease of body temperature.Conclusion-Only low-dosage ovalbumin feedings under anti-acid medication resulted in IgE mediated food allergy. Based on this knowledge we have established a suitable food allergy model for further investigations of food adverse reactions.

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Section: Discussionmentioning

confidence: 96%

Section: Ova Feeding Under Acid-suppression Induces Antigen-specific mentioning

confidence: 99%

Dose-dependent food allergy induction against ovalbumin under acid-suppression: A murine food allergy model

et al. 2008

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“…High total and food-specific IgE serum levels were detected in patients with peptic ulcers treated with antiulcer medication [29] and in sensitized mice treated with acid suppressors [30]. It was firstly attributed to the aluminum compound present in the antacid drugs [31]; however, it is accepted that gastric digestive capacity is the main factor to alter the allergenic capacity of ingested food proteins due to their native conformation.…”

Section: Discussionmentioning

confidence: 99%

In vivo Evidence of Cross-Reactivity between Cow’s Milk and Soybean Proteins in a Mouse Model of Food Allergy

Smaldini¹,

Curciarello²,

Candreva³

et al. 2012

Int Arch Allergy Immunol

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Background: Cow’s milk allergy (CMA) is an important problem worldwide and the development of an in vivo system to study new immunotherapeutic strategies is of interest. Intolerance to soybean formula has been described in CMA patients, but it is not fully understood. In this work, we used a food allergy model in BALB/c mice to study the cross-reactivity between cow’s milk protein (CMP) and soy proteins (SP). Methods: Mice were orally sensitized with cholera toxin and CMP, and then challenged with CMP or SP to induce allergy. Elicited symptoms, plasma histamine, humoral and cellular immune response were analyzed. Th1- and Th2-associated cytokines and transcription factors were assessed at mucosal sites and in splenocytes. Cutaneous tests were also performed. Results: We found that the immediate symptoms elicited in CMP-sensitized mice orally challenged with SP were consistent with a plasma histamine increase. The serum levels of CMP-specific IgE and IgG1 antibodies were increased. These antibodies also recognized soy proteins. Splenocytes and mesenteric lymph node cells incubated with CMP or SP secreted IL-5 and IL-13. mRNA expression of Th2-associated genes (IL-5, IL-13, and GATA-3) was upregulated in mucosal samples. In addition, sensitized animals exhibited positive cutaneous tests after the injection of CMP or SP. Conclusions: We demonstrate that CMP-sensitized mice, without previous exposure to soy proteins, elicited hypersensitivity signs immediately after the oral administration of SP, suggesting that the immunochemical cross-reactivity might be clinically relevant. This model may provide an approach to further characterize cross-allergenicity phenomena and develop new immunotherapeutic treatments for allergic patients.

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“…Additionally, sucralfate, but also simple antacids are aluminum containing drugs, which might per se exert a substantial in uence on the immune response [49]. Despite common knowledge, the rst focused study evaluating the impact of the aluminum containing drug sucralfate on the immune response appeared in 2007. e authors revealed a T helper cell 2 ( 2) shi a er systemic application in an experimental model and speculated on a possible impact of aluminum on the observed immune response deviation [50]. e biogenic amine histamine exerts an e ect on a large variety of di erent cells including important immune cells via its four receptors [51].…”

Section: Acid Suppression Medication and The Immune Responsementioning

confidence: 99%

Acid suppression therapy and allergic reactions

Untersmayr¹

2015

Allergo J

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e development of pharmaceutical agents reducing gastric acidity such as sucralfate, histamine 2 (H2) receptor blockers, and proton pump inhibitors (PPIs) has been a milestone for the treatment of dyspeptic disorders. However, due to current prescription habits resulting in overuse of these potent drugs as well as over-the-counter (OTC) availability associated with self-medication, substantial health concern is related to the mechanisms of drug action as well as known side e ects in uencing gastrointestinal physiology. More than a decade ago, the rst study appeared reporting an association between anti-ulcer drug intake and food allergy development. Since then, several experimental and human studies veri ed this correlation, demonstrating that acid suppressive drugs not only in uence the sensitization capacity of orally ingested proteins, but also represent a risk factor for food allergic patients. Additionally, gastric acid suppression was reported to increase the risk for development of drug hypersensitivity reactions. ese consequences of anti-ulcer drug intake might on the one hand be associated with direct in uence of these drugs on immune responses. On the other hand reduction of gastric acidity leads to impaired gastrointestinal protein degradation. Nevertheless, also disruption of the gastrointestinal barrier function, changes in microbiome, or lack of tolerogenic peptic digests might contribute to the connection between anti-ulcer drug intake and allergic reaction. erefore, these drugs should only be prescribed based on a precise gastroenterological diagnosis taking into consideration allergological mechanisms to ensure patients' safety.Cite this as: Untersmayr E. Acid suppression therapy and allergic reactions.

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The impact of aluminium in acid‐suppressing drugs on the immune response of BALB/c mice

Cited by 37 publications

References 34 publications

Dose-dependent food allergy induction against ovalbumin under acid-suppression: A murine food allergy model

Dose-dependent food allergy induction against ovalbumin under acid-suppression: A murine food allergy model

In vivo Evidence of Cross-Reactivity between Cow’s Milk and Soybean Proteins in a Mouse Model of Food Allergy

Acid suppression therapy and allergic reactions

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