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
  • Smooth muscle relaxation
  • Smooth muscle relaxation
  • Inflammation
    • Raises body temperature
    • Increases sensitivity to pain
  • Metabolism
    • Inhibits lipolysis
  • Stomach
  • Analog: dinoprostone
    • Cervical ripening
  • Smooth muscle contraction
  • 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.
last updated 11/20/2018
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