Origin and Function of Interleukins
- The term interleukin is derived from:
- “Inter,” which means between or among
- “Leukin,” which is the origin of the word “leukocyte”
- Together, the word interleukin refers to a molecule that plays a role in communication between the cellular constituents of the immune system.
- The primary function of ILs is to modulate the growth, differentiation, and activation of immune cells during inflammatory and immune responses.
- ILs play a role in both innate and adaptive immune responses.
- ILs are produced in response to:
- Other ILs
- ILs influence the synthesis and actions of other ILs (e.g., IL-1 stimulates IL-2 release).
- Only very small quantities of ILs are needed to occupy receptors and elicit biological effects.
- ILs are a diverse group of molecules with differing protein structures.
- Approximately 35 ILs have been identified and described.
|Name||Source||Target cells||Effect on target cells|
|IL-7||Differentiation and proliferation of lymphoid progenitor cells|
|IL-14||T cells||B cells|
|IL-16||CD4+ T cells||CD4+ chemoattraction|
|IL-22||T cells||Epithelial cells|
|IL-23||T cells||Maintenance of IL-17 producing cells|
|IL-26||T cells||Induces secretion of IL-10 and IL-8|
|IL-27||Upregulation of proinflammatory cytokines|
|IL-28||Plays a role in immune defense against viruses|
|IL-29||Plays a role in immune defense against microbes|
|IL-30||May play a role in tumor growth|
|IL-32||Induces cytokine and chemokine production|
|IL-34||Differentiation, migration, and survival of antigen-presenting cells|
TNF: tumor necrosis factor
Th: T helper
Clinically Relevant Interleukins
- Important for stimulating T helper (Th)1 immune response:
- Fights intracellular pathogens (e.g., viruses)
- Important for tumor surveillance
- Becomes overactive in autoimmune conditions
- Can be administered pharmacologically:
- Immunotherapy to treat patients with cancer (melanoma and renal carcinoma)
- Has been used in clinical trials to increase CD4 counts in patients who are HIV positive
- Adverse effects:
- GI upset
Interleukin-4 and IL-5
- Together, IL-4 and IL-5 play an important role in IgE-mediated allergic responses.
- Stimulates IgE synthesis
- Increases the adherence and passage of lymphocytes through the endothelium
- IL-5 stimulates eosinophil production.
- Medical targets: Dupilumab is a monoclonal antibody that targets the IL-4 receptor; it has been approved by the FDA to treat asthma and atopic dermatitis.
- Acute-phase reactant
- Produced by the liver in response to infection or physiologic stress
- Stimulates innate and adaptive immune responses
Interleukin-12, IL-17, and IL-23
- Play an important role in the pathogenesis of psoriasis
- Targets of monoclonal antibodies used to treat psoriasis
- Akdis, M., et al. (2011). Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 127(3), 701-21.e1–70. https://pubmed.ncbi.nlm.nih.gov/21377040/
- Zhu, Z., et al. (2017). Bioinformatics analyses of pathways and gene predictions in IL-1α and IL-1β knockout mice with spinal cord injury. Acta Histochem. 119(7), 663–670. https://pubmed.ncbi.nlm.nih.gov/28851482/
- Boraschi, D., et al. (1996). Structure-function relationship in the IL-1 family. Front Biosci. 1, d270–308. https://pubmed.ncbi.nlm.nih.gov/9159234/
- Arend, W.P., et al. (1998). Interleukin-1 receptor antagonist: Role in biology. Annu Rev Immunol. 16, 27–55. https://pubmed.ncbi.nlm.nih.gov/9597123/
- Dinarello, C.A. (2018). Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 281(1), 8–27. https://pubmed.ncbi.nlm.nih.gov/29247995/
- Bachmann, M.F., Oxenius, A. (2007). Interleukin 2: From immunostimulation to immunoregulation and back again. EMBO Rep. 8(12), 1142–1148. https://pubmed.ncbi.nlm.nih.gov/18059313/
- Ghiasi, H., et al. (1999). The role of interleukin (IL)-2 and IL-4 in herpes simplex virus type 1 ocular replication and eye disease. J Infect Dis. 179(5), 1086–1093. https://pubmed.ncbi.nlm.nih.gov/10191208/
- Eder, M., Geissler, G., Ganser, A. (1997). IL-3 in the clinic. Stem Cells. 15(5), 327–333. https://pubmed.ncbi.nlm.nih.gov/9323793/
- Frendl, G. (1992). Interleukin 3: From colony-stimulating factor to pluripotent immunoregulatory cytokine. Int J Immunopharmacol. 14(3), 421–430. https://pubmed.ncbi.nlm.nih.gov/1618595/
- Belghith, M., et al. (2018). Cerebrospinal fluid IL-10 as an early stage discriminative marker between multiple sclerosis and neuro-Behçet disease. Cytokine. 108, 160–167. https://pubmed.ncbi.nlm.nih.gov/29625335/
- Couper, K.N., Blount, D.G., Riley, E.M. (2008). IL-10: The master regulator of immunity to infection. J Immunol. 180(9), 5771–5777. https://pubmed.ncbi.nlm.nih.gov/18424693/
- Jiang, T., et al. (2018). miR‑23b inhibits proliferation of SMMC‑7721 cells by directly targeting IL‑11. Mol Med Rep. 18(2), 1591–1599. https://pubmed.ncbi.nlm.nih.gov/29901200/
- Zhang, J.H., et al. (2019). Correlation between IL-4 and IL-13 gene polymorphisms and asthma in Uygur children in Xinjiang. Exp Ther Med. 17(2), 1374–1382. https://pubmed.ncbi.nlm.nih.gov/30680016/
- Dhaouadi, T., et al. (2018). IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis. PLoS One. 13(3), e0194883. https://pubmed.ncbi.nlm.nih.gov/29584788/
- Guerra, E.S., et al. (2017). Central role of IL-23 and IL-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma. PLoS Pathog. 13(1), e1006175. https://pubmed.ncbi.nlm.nih.gov/28095479/
- Gabunia, K., Autieri, M.V. (2015). Interleukin-19 can enhance angiogenesis by macrophage polarization. Macrophage (Houst). 2(1), e562. https://pubmed.ncbi.nlm.nih.gov/26029742/
- Lin, P.Y., et al. (2015). Interleukin-21 suppresses the differentiation and functions of T helper 2 cells. Immunology. 144(4), 668–676. https://pubmed.ncbi.nlm.nih.gov/25351608/
- Shabgah, A.G., et al. (2017). Interleukin-22 in human inflammatory diseases and viral infections. Autoimmun Rev. 16(12), 1209–1218. https://pubmed.ncbi.nlm.nih.gov/29037907/
- Wang, X., et al. (2016). A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in lupus-like mice. Eur J Immunol. 46(6), 1343–1350. https://pubmed.ncbi.nlm.nih.gov/27019190/
- Catalan-Dibene, J., et al. (2017). Identification of IL-40, a novel B cell-associated cytokine. J Immunol. 199(9), 3326–3335. https://pubmed.ncbi.nlm.nih.gov/28978694/
- Li, Y., et al. (2019). Elevated serum IL-35 levels in rheumatoid arthritis are associated with disease activity. J Investig Med. 67(3), 707–710. https://pubmed.ncbi.nlm.nih.gov/30659089/