Cytokines

Overview

Cytokines are signaling proteins that act on receptors and regulate the activation of cell differentiation, especially in the immune system.

Interleukins

  • Interleukins are a group of signaling proteins that regulate immune response as well as cellular proliferation and differentiation.
  • Each group of interleukins acts on a specific group of cells.
  • There are currently 38 known interleukins, the most important of which are listed below.
Interleukin Secreted by

Targets and effect

Interleukin-1 (IL-1)
Interleukin-2 (IL-2)
Interleukin-3 (IL-3)
Interleukin-4 (IL-4)
Interleukin-5 (IL-5)
Interleukin-6 (IL-6)
Interleukin-7 (IL-7)
Interleukin-8 (IL-8)
Interleukin-10 (IL-10)
Interleukin-11 (IL-11)
Interleukin-12 (IL-12)
  • Activates natural killer (NK) cells
  • Promotes differentiation of naive T cells into Th1 cells.
Interleukin-24 (IL-24)

Interleukin-28 (IL-28)

Interleukin-29 (IL-29)

  • Dendritic cells
  • Antiviral immunity
Interleukin-32 (IL-32)



Interleukins secreted by macrophages: IL-1, 6, 8, 12 (and TNF-α)
Interleukins secreted by all T cells: IL-2 and 3
Most important proinflammatory interleukins (endogenous pyrogens and main mediators of sepsis): IL-1 and 6 (and TNF-α)
Most important anti-inflammatory interleukin: IL-10
Promoters of differentiation of T cells to Th2: IL-2 and 4
Class switching interleukins: IL-4 and 5
Acute phase reactant stimulators: IL-6 and 11
Neutrophil chemotactic factor: IL-8 (chemokine)

Interferons and tumor necrosis factor

Interferons

  • Interferons are cell signaling proteins that are secreted by cells infected by viruses, bacteria, or parasites, as well as by leukocytes and fibroblasts in response to infection or neoplastic proliferation.
  • They have antiviral, antimicrobial, and antitumor (antiproliferative) properties and are a part of the innate immune system.
  • Because of these properties, interferons are used in the treatment of chronic infections (hepatitis B and C, chronic granulomatous diseases), immune-mediated diseases (multiple sclerosis), and even tumors (leukemia, Kaposi sarcoma)
  • There are three major classes of interferons, which are listed below.
Interferon Secreted by Function

Therapeutic use

Interferon alpha (IFN-α)
  • Virus‑infected cells and malignant cells, especially leukocytes
  • First line of defense against all viral infections
  • Inhibits viral protein synthesis by activating ribonuclease L (leads to the degradation of cellular and viral mRNA)
  • Promotes the expression of MHC class I molecules activation of NK cells and cytotoxic T cells
  • Inhibits megakaryocyte stem cell differentiation and proliferation
Interferon beta (IFN-β)
Interferon gamma (IFN-γ)
  • Activates macrophages to increase phagocytosis (positive reinforcement)
  • Formation of granulomas (critical against mycobacterial infections)
  • Suppresses a Th2 response (negative feedback)
  • Promotes the expression of MHC class II molecules

Tumor necrosis factor

Secreted by Functions Therapeutic use
Tumor necrosis factor alpha (TNF-α; cachectin)
  • Pyrogenic
  • Cytotoxic and inhibits carcinogenesis of certain tumors
  • Mediates septic shock
  • Cause of malignant cachexia
  • Maintenance of granulomas (critical defense against mycobacterial infections)
  • TNF‑α inhibitors such as infliximab are used in the treatment of refractory chronic inflammatory systemic diseases (e.g., Crohn disease).

Tumor necrosis factor beta (TNF-β; lymphotoxin)

Th1 lymphocytes secrete IFN-γ, which activates macrophages and is essential for the formation of tubercular granulomas.
Activated macrophages secrete TNF-α, which is essential for the maintenance of tubercular granulomas.

References:[1]

Eicosanoids

Enzyme Intermediate Eicosanoid Function

Clinical relevance

(analogs and inhibitors)

Arachidonic acid
  • 5-lipoxygenase
  • Bronchoconstriction
  • Increased capillary permeability
  • COX-1 and COX-2
  • Vasoconstriction
  • Promotes platelet aggregation
  • Vasodilation
  • Inhibits platelet aggregation

  • 1. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P . Molecular Biology of the Cell. New York, NY: Garland Science; 2002.
  • Lebrec H, Ponce R, Preston BD, Iles J, Born TL, Hooper M. Tumor necrosis factor, tumor necrosis factor inhibition, and cancer risk. Curr Med Res Opin. 2015; 31(3): pp. 557–574. doi: 10.1185/03007995.2015.1011778.
  • Drutskaya MS, Efimov GA, Kruglov AA, Kuprash DV, Nedospasov SA. Tumor necrosis factor, lymphotoxin and cancer. Life. 2010; 62(4): pp. 283–289. doi: 10.1002/iub.309.
  • Dembic Z. The Cytokines of the Immune System. Academic Press; 2015.
  • Lin PL, Plessner HL, Voitenok NN, Flynn JL. Tumor necrosis factor and tuberculosis. J Investig Dermatol Symp Proc. 2007; 12(1): pp. 22–25. doi: 10.1038/sj.jidsymp.5650027.
  • Harris J, Keane J. How tumour necrosis factor blockers interfere with tuberculosis immunity. Clin Exp Immunol. 2010; 161(1): pp. 1–9. doi: 10.1111/j.1365-2249.2010.04146.x.
  • Hong S. Connection between inflammation and carcinogenesis in gastrointestinal tract: Focus on TGF-β signaling. World J Gastroenterol. 2010; 16(17): p. 2080. doi: 10.3748/wjg.v16.i17.2080.
  • Long R, Gardam M. Tumour necrosis factor-alpha inhibitors and the reactivation of latent tuberculosis infection. CMAJ. 2003; 168(9): pp. 1153–6. pmid: 12719321.
  • Parkin J, Cohen B. An overview of the immune system. Lancet. 2001; 357(9270): pp. 1777–1789. doi: 10.1016/s0140-6736(00)04904-7.
  • Li D. Cell-Mediated Immunity. https://step1.medbullets.com/immunology/105050/cell-mediated-immunity. Updated November 17, 2018. Accessed December 30, 2018.
  • Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest. 2000; 117(4): pp. 1162–1172. doi: 10.1378/chest.117.4.1162.
  • Berger A. Science commentary: Th1 and Th2 responses: what are they?. BMJ. 2000; 321(7258): pp. 424–424. doi: 10.1136/bmj.321.7258.424.
  • Panchbhavi VK. Bone Marrow Anatomy. In: Gest TR. Bone Marrow Anatomy. New York, NY: WebMD. https://emedicine.medscape.com/article/1968326. Updated November 29, 2017. Accessed December 19, 2017.
  • Sino Biological. Anti-Inflammatory Cytokines List. http://www.sinobiological.com/Anti-inflammatory-cytokines-list.html. Updated January 1, 2018. Accessed December 30, 2018.
  • Sino Biological. Interleukin Function / Function of Interleukin. http://www.sinobiological.com/interleukin-function-function-of-interleukin.html. Updated January 1, 2018. Accessed December 30, 2018.
  • Kaplan. USMLE Step 1 Lecture Notes 2016: Immunology and Microbiology. Kaplan Publishing; 2015.
  • Akdis M, Burgler S, Crameri R, et al. Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2011; 127(3): pp. 701–721.e70. doi: 10.1016/j.jaci.2010.11.050.
  • Sims NA, Jenkins BJ, Nakamura A, et al. Interleukin-11 receptor signaling is required for normal bone remodeling. J Bone Miner Res. 2005; 20(7): pp. 1093–1102. doi: 10.1359/jbmr.050209.
last updated 02/11/2019
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