Interleukin-13

Interleukin-13 (IL-13) is a pleiotropic immunoregulatory cytokine that acts via the IL13Ra1/IL4Ra receptor complex. Its functions are comparable to those of interleukin-4, as both cytokines share the same receptor. Interleukin-13 has only a weak affinity to its receptor. High affinity binding is only achieved through co-expression with the interleukin-4 receptor. In addition to 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 influences numerous cell types such as B cells, monocytes, NK cells, endothelial cells and fibroblasts. IL-13 also inhibits the activation of macrophages.

The cytokine inhibits the release and function of pro-inflammatory 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, acting in addition to interleukin-4. Together with interleukin-4, interleukin-13 plays a role in the defense against intestinal nematode infections.

Interleukin-13 is massively expressed in cutaneous radiation syndrome and plays an etiopathogenetically significant role in radiation fibrosis.

Overexpression of interleukin-13 and its receptor has been demonstrated in a number of malignant tumors (glioblastoma, colorectal carcinoma). Various therapy regimes were derived from these observations.

Interleukin-13 plays a pioneering 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.

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