Printed From:

IN ATOPIC DERMATITIS, KEY TH2 CYTOKINES MAY BE AT THE CORE OF PERSISTENT,
UNDERLYING INFLAMMATION

Th2 cytokines IL-4 and IL-13 are key drivers involved with the underlying inflammatory process1

Current evidence has shown that nonlesional skin is not normal skin, owing to persistent subclinical inflammation throughout the body.1-4 This underlying inflammation is a source of the primary signs and symptoms of atopic dermatitis.1,3,4 Th2 dominance in tissue samples from patients with atopic dermatitis is well documented, with Th2-specific cytokines dominating the immune infiltrate.5

Studies of tissue samples from patients with atopic dermatitis have shown that acute and chronic lesions, as well as nonlesional skin, are associated with an increased1,6-9:

  • Number of immune cells that secrete IL-4 and IL-13
  • Amount of Th2 signaling, compared with samples from healthy controls

Explore the Th2 pathway by tapping the following icons:

IL-4 and IL-13 Cytokines in Th2 Signaling IL-4 and IL-13 Cytokines in Th2 Signaling IL-4 and IL-13 Cytokines in Th2 Signaling
IL-4 and IL-13 Cytokines in Th2 Signaling IL-4 and IL-13 Cytokines in Th2 Signaling IL-4 and IL-13 Cytokines in Th2 Signaling IL-4 and IL-13 Cytokines in Th2 Signaling
IL-4 and IL-13 Cytokines in Th2 Signaling IL-4 and IL-13 Cytokines in Th2 Signaling IL-4 and IL-13 Cytokines in Th2 Signaling

Animal and human studies have shown that IL-4 and IL-13 may be the key drivers of a systemic, chronic inflammatory response.13 Research in animal and in vitro models has demonstrated:

  • IL-13 is considered to be an “effector” cytokine with distinct but overlapping roles from IL-4 in both the normal immune response to parasitic infections and the pathogenesis of atopic dermatitis14
transcript ▼

This has increased my understanding of the mechanism of underlying inflammation

References: 1. Gittler JK, Shemer A, Suárez-Fariñas M, et al. Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344-1354. 2. De Benedetto A, Rafaels NM, McGirt LY, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786. 3. Leung DYM, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004;113(5):651-657. 4. Suárez-Fariñas M, Tintle SJ, Shemer A, et al. Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities. J Allergy Clin Immunol. 2011;127(4):954-964. 5. Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis─Part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol. 2011;127(6):1420-1432. 6. Hamid Q, Boguniewicz M, Leung DYM. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest. 1994;94(2):870-876. 7. Lonati A, Licenziati S, Canaris AD, et al. Reduced production of both Th1 and Tc1 lymphocyte subsets in atopic dermatitis (AD). Clin Exp Immunol. 1999;115(1):1-5. 8. Tazawa T, Sugiura H, Sugiura Y, Uehara M. Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch Dermatol Res. 2004;295(11):459-464. 9. Novak N, Bieber T, Leung DYM. Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol. 2003;112(6 suppl):S128-S139. 10. Noda S, Kruger JG, Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases. J Allergy Clin Immunol. 2015;135(2):324-336. 11. Guttman-Yassky E, Dhingra N, Leung DYM. New era of biological therapeutics in atopic dermatitis. Expert Opin Biol Ther. 2013;13(4):549-561. 12. Biedermann T, Skabytska Y, Kaesler S, Volz T. Regulation of T cell immunity in atopic dermatitis by microbes: the yin and yang of cutaneous inflammation. Front Immunol. 2015;6:353. doi:10.3389/fimmu.2015.00353 13. Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011;2(3):1-25. 14. Junttila IS, Mizukami K, Dickensheets H, et al. Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Rɑ, IL-13Rɑ1, and γc regulates relative cytokine sensitivity. J Exp Med. 2008;205(11):2595-2608. 15. Haas H,Falcone FH, Holland MJ, et al. Early interleukin-4: its role in the switch towards a Th2 response and IgE-mediated allergy. int Arch Allergy Immunol. 1999;119(2):86-94. 16. Le Gros G,Ben-Sasson SZ, Seder R,Finkelman FD, Paul WE. Generation of interleukin 4(IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med. 1990;172(3):921-929. 17. Stott B, Lavender P, Lehmann S, Pennino D, Durham S, Schmidt-Weber CB. Human IL-31 is induced by IL-4 and promotes Th2-driven inflammation. J Allergy Clin Immunol. 2013;132(2):446-454.