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Cytokine & Chemokines in Disease: Allergies

Cytokines and chemokines are key modulators of immune responses and play diverse roles in inflammatory diseases. Here, we discuss the role of specific cytokines and chemokines in allergies and hypersensitivity reactions.

Chondrex Inc., is committed to enabling inflammatory research worldwide by providing a variety of animal models and detection assays for your study needs. Please visit our Cytokine & Chemokine Detection ELISA Kits page for a complete list of the ELISA kits we offer and suggested animal models for your research needs.

Allergies and Hypersensitivity Reactions

Allergens, whether from food, air pollution, dust mites, pet dander, or mold, can induce hypersensitivity reactions mediated by IgE antibodies. An outcome of an allergic reaction is an asthmatic response characterized by airflow obstruction and bronchospasm. In allergic responses, T-Helper cells induce expression of many cytokines including TNF-α, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-13 (1-4).  Of these cytokines, IL-4 and IL-13 play critical roles in the allergic response. IL-13 has a distinctive role in mucus production, while IL-4 has been found to be the major driver of IgE and IgG1 synthesis by B-Cells (5,6). Furthermore, IL-5 drives blood and tissue eosinophilia, a characteristic feature of allergic reactions (5,6). 

To study asthmatic responses, ovalbumin (OVA) and house dust mite (HDM) are widely used antigens for inducing allergic responses (1,2,6,7). Both the OVA-Induced Asthma Model and the HDM-Induced Asthma Model can elicit airway inflammation, which can lead to airflow obstruction and airway remodeling (AR). AR is due to increased deposition of collagen and elastic fibers in airway passages, as well as hypertrophy and hyperplasia of the airway smooth muscle cells. This results in the thickening of the airway walls and narrowing of the passage. AR maintenance is primarily regulated by vascular endothelial growth factor (VEGF) and transforming growing factor-beta (TGF-β) activity. Mouse models show that during an allergic reaction, VEGF and TGF-β are upregulated and promote pathological AR (3-6).

There are many chemokines associated with allergic reactions, including CCL11, CCL17 and CCL22 which have all been found upregulated in the broncho-alveolar lavage of patients with asthma. In a murine model, it has been shown that the suppression of CCL11 decreased eosinophil recruitment and reduced airway hyper-responsiveness. Indeed, asthmatic patient samples displayed higher levels of CCL11 in plasma than healthy volunteers. Chemokines CCL17 and CCL22 bind to CCR4 which is expressed mostly by Th2 cells and play a major role in the recruitment of T cells both in mice and in humans. CCL17 and CCL22 are well documented in many allergic reactions including skin and food allergies (6,8).

Qian et al., tested possible mechanisms on how LPS exposure can desensitize allergic responses, specifically Th2 immune mechanisms. To test their hypothesis the group used Chondrex Inc.'s low endotoxin OVA on transgenic mice to characterize the cellular and cytokine profile of the allergic response. Chondrex Inc, low endotoxin OVA led to upregulation of multiple immune cells including eosinophils, neutrophils and lymphocytes. In addition, IL-4, IL-5, IL-13 and INF-γ which are Th1/Th2 cytokines, were upregulated (9).

Several other methods are used for inducing experimental allergic responses, including immunization with Mouse Anti-OVA IgE and IgG Monoclonal Antibodies and House Dust Mite Extract. To learn more about these models and their unique features, follow the links above.    

References

  1. A. Nials, S. Uddin, Mouse models of allergic asthma: acute and chronic allergen challenge. Dis Model Mech 1, 213-20 (2008).
  2. V. Gandhi, C. Davidson, M. Asaduzzaman, D. Nahirney, H. Vliagoftis, House dust mite interactions with airway epithelium: role in allergic airway inflammation. Curr Allergy Asthma Rep 13, 262-70 (2013).
  3. R. Silva, F. Almeida, C. Olivo, B. Saraiva-Romanholo, M. Martins, C. Carvalho, et al., Exercise reverses OVA-induced inhibition of glucocorticoid receptor and increases anti-inflammatory cytokines in asthma. Scand J Med Sci Sports 26, 82-92 (2016).
  4. F. Vuolo, F. Petronilho, B. Sonai, C. Ritter, J. Hallak, et al., Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma. Mediators Inflamm 2015, 538670 (2015).
  5. B. Lambrecht, H. Hammad, J. Fahy, The Cytokines of Asthma. Immunity 50, 975-991 (2019).
  6. L. Castan, A. Magnan, G. Bouchaud, Chemokine receptors in allergic diseases. Allergy 72, 682-690 (2017).
  7. J. Kim, H. Kim, Y. Im, Y. Bae, S. Im, H. Lee, et al., FcyR/ROS/CK2α Is the Key Inducer of NF-κB Activation in a Murine Model of Asthma. Int Arch Allergy Immunol 175, 16-25 (2018).
  8. A. Knight, A. Blázquez, S. Zhang, L. Mayer, H. Sampson, M. Berin, et al., CD4 T cells activated in the mesenteric lymph node mediate gastrointestinal food allergy in mice. Am J Physiol Gastrointest Liver Physiol 293, G1234-43 (2007).
  9. G. Qian, W. Jiang, B. Zou, J. Feng, X. Cheng, et al., LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma. J Exp Med 215, 2397-2412 (2018).