Interleukin-13

Interleukin-13 (IL-13) is a pleiotropic immunoregulatory cytokine that acts via the IL-13Ra1/IL-4Ra complex. Its functions are similar to those of interleukin-4, and both cytokines share the same receptor. Interleukin-13 has only a weak affinity to its receptor. A high-affinity binding is only achieved by co-expression with the interleukin-4 receptor. Besides the membrane-bound receptor, soluble sIL-13R is also detected.

The gene coding for interleukin-13 is located on chromosome 5 .

Interleukin-13 is produced by activated CD8- and CD4-positive T lymphocytes. Interleukin (IL)-13 affects numerous cell types such as B cells, monocytes, NK cells, endothelial cells, and fibroblasts. Furthermore, IL-13 inhibits the activation of macrophages.

The cytokine inhibits the release and function of proinflammatory cytokines(interleukin-1, interleukin-6, interleukin-8, interleukin-10, interleukin-13) and TNFalpha. Furthermore, the production of nitric oxide (NO) by macrophages is reduced. In addition, the expression of class II MHC antigens is promoted. The cytokine induces and maintains fibrosing processes whereby it acts additively to interleukin-4. Interleukin-13, together with interleukin-4, plays a role in the defense against intestinal nematode infections.

Overexpression of interleukin-13 and its receptor has been demonstrated in a number of malignant tumors (glioblastoma, colorectal carcinoma). From these observations, different therapeutic regimens have been derived.

Interleukin-13 has a seminal role in diseases such as bronchial asthma and atopic eczema, as well as in progressive systemic scleroderma.

The targeted neutralization of IL-13(tralokizumab) led to a consistently high positive response rate in patients with moderate to severe atopic dermatitis (Langley R et al. 2022).

Lebrikizumab (preparation Ebglyss®), a high-affinity monoclonal antibody, also selectively binds to soluble interleukin-13 (IL-13). It thereby prevents the formation of the IL-13Rα1/IL-4Rα heterodimer complex and subsequent signal transmission. Lebrikizumab is indicated for the treatment of moderate to severe atopic dermatitis in adults and adolescents aged twelve years and older weighing at least 40 kg who are eligible for systemic therapy.

The simultaneous blockade of interleukins (IL)-4 and IL-13 leads to a suppression of the clinical symptoms of bronchial asthma and atopic dermatitis. Dupilumab is a monoclonal antibody directed against the alpha chain of interleukins-13 and -4, which inhibits the function of both interleukins. Dupilumab has already demonstrated its efficacy in clinical trials in both bronchial asthma and atopic dermatitis.

1. Buzney CD et al.(2016) Asthma and Atopic Dermatitis: A Review of Targeted Inhibition of Interleukin-4 and Interleukin-13 As Therapy for Atopic Disease. J Drugs Dermatol 15:165-171.
2. Corren J (2013) Role of interleukin-13 in asthma. Curr Allergy Asthma Rep 13:415-420.
3. Finkelman FD et al (2004) Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites.Immunol Rev 201:139-155.
4. Hess C et al. (2015) The antibody-mediated targeted delivery of interleukin-13 to syngeneic murine tumors mediates a potent anticancer activity. Cancer Immunol Immunother 64:635-644.
5. Joshi BH et al.(2006) Role of interleukin-13 in cancer, pulmonary fibrosis, and other T(H)2-type diseases. Vitam Horm 74:479-504.
6. Kuperman DA et al (2008) Interleukin-4, interleukin-13, signal transducer and activator of transcription factor 6, and allergic asthma. Curr Mol Med 8:384-392.
7. Langley R et al (2022) Poster presemted at: 4th Annual Revolutionizing Atopic Dermatitis Conference, April 9-11.
8. O'Reilly S (2013) Role of interleukin-13 in fibrosis, particularly systemic sclerosis. Biofactors 39:593-596.
9. Rayees S et al.(2014) Linking GATA-3 and interleukin-13: implications in asthma. Inflamm Res 63:255-265.
10. Seyfizadeh N et al. (2015) Interleukin-13 as an important cytokine: A review on its roles in some human diseases. Acta Microbiol Immunol Hung 62:341-378.
11. Wills-Karp M (2004) Interleukin-13 in asthma pathogenesis. Immunol Rev 202:175-190.
12. Zhou R et al.(2013) Interleukin-13 and its receptors in colorectal cancer (Review). Biomed Rep 1:687-690.