Interleukin 4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell. It is closely related and has functions similar to Interleukin 13.
Tissue macrophages play an important role in chronic inflammation and wound repair. The presence of IL-4 in extravascular tissues promotes alternative activation of macrophages into M2 cells and inhibits classical activation of macrophages into M1 cells. An increase in repair macrophages (M2) is coupled with secretion of IL-10 and TGF-β that result in a diminution of pathological inflammation. Release of arginase, proline, polyaminases and TGF-β by the activated M2 cell is tied with wound repair and fibrosis.
The receptor for Interleukin-4 is known as the IL-4Rα. This receptor exists in 3 different complexes throughout the body. Type 1 receptors are composed of the IL-4Rα subunit with a common γ chain and specifically bind IL-4. Type 2 receptors consist of an IL-4Rα subunit bound to either another IL-4Rα, or a different subunit known as IL-13Rα1. These type 2 receptors have the ability to bind both IL-4 and IL-13, two cytokines with closely related biological functions.
^Sokol, C.L., Barton, G.M., Farr, A.G. & Medzhitov, R. (2008). "A mechanism for the initiation of allergen-induced T helper type 2 responses". Nat Immunol9 (3): 310–318. doi:10.1038/ni1558. PMID18300366.
^Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA (December 1997). "The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor". N. Engl. J. Med.337 (24): 1720–5. doi:10.1056/NEJM199712113372403. PMID9392697. Lay summary – eurekalert.org.
^Jon Aster, Vinay Kumar, Abul K. Abbas; Nelson Fausto (2009). Robbins & Cotran Pathologic Basis of Disease (8th ed.). Philadelphia: Saunders. p. 54. ISBN1-4160-3121-9.
Kay AB, Barata L, Meng Q, et al. (1997). "Eosinophils and eosinophil-associated cytokines in allergic inflammation". Int. Arch. Allergy Immunol.113 (1–3): 196–9. doi:10.1159/000237545. PMID9130521.
Marone G, Florio G, Petraroli A, de Paulis A (2001). "Dysregulation of the IgE/Fc epsilon RI network in HIV-1 infection". J. Allergy Clin. Immunol.107 (1): 22–30. doi:10.1067/mai.2001.111589. PMID11149986.
Marone G, Florio G, Triggiani M, et al. (2001). "Mechanisms of IgE elevation in HIV-1 infection". Crit. Rev. Immunol.20 (6): 477–96. PMID11396683.
Maeda S, Yanagihara Y (2001). "[Inflammatory cytokines (IL-4, IL-5 and IL-13)]". Nippon Rinsho59 (10): 1894–9. PMID11676128.
Izuhara K, Arima K, Yasunaga S (2003). "IL-4 and IL-13: their pathological roles in allergic diseases and their potential in developing new therapies". Current drug targets. Inflammation and allergy1 (3): 263–9. doi:10.2174/1568010023344661. PMID14561191.
Olver S, Apte S, Baz A, Kienzle N (2007). "The duplicitous effects of interleukin 4 on tumour immunity: how can the same cytokine improve or impair control of tumour growth?". Tissue Antigens69 (4): 293–8. doi:10.1111/j.1399-0039.2007.00831.x. PMID17389011.