Cytokines are signaling proteins that modulate immune responses, inflammation, and hematopoietic cell proliferation and differentiation. They are mainly secreted by hematopoietic cells and can act in an autocrine, paracrine, or endocrine mode. They are classified into proinflammatory cytokines (interleukins 1, 6, 8, 12, and 18; interferons; and tumor necrosis factor) and anti-inflammatory cytokines (interleukins 4,10, 11, and 13; and transforming growth factor-beta). Proinflammatory cytokines induce fever and inflammation in response to infection or tissue injury, while anti-inflammatory cytokines suppress the immune system. Interferons are proinflammatory cytokines that are secreted by fibroblasts, leukocytes, cells infected by viruses in response to infection or neoplastic proliferation. Since interferons have antiviral, antimicrobial, and antitumor (antiproliferative) properties, they are used in the treatment of chronic viral infections (hepatitis B and hepatitis C), tumors (leukemia, Kaposi sarcoma), and autoimmune diseases (rheumatoid arthritis, systemic sclerosis).
- proteins that are secreted mainly by hematopoietic cells (esp. T lymphocytes) in response to a stimulus such as infection, ischemia, or injury. are small extracellular signaling
- They modulate immune responses, inflammation, and hematopoietic cellular proliferation and differentiation.
- Target receptors are located on:
- Functional classification of cytokines
- Proinflammatory cytokines (Th1 cytokines): stimulate the immune system
- Anti-inflammatory cytokines (Th2 cytokines): suppress the immune system
- An imbalance between the proinflammatory and anti-inflammatory cytokine response is responsible for several immune-mediated diseases (e.g., , , ).
- proteins that regulate immune response as well as cellular proliferation and differentiation. are a group of signaling
- 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-11 (IL-11)|| |
|Interleukin-24 (IL-24)|| |
| || |
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)
Hot T-bone stEAK represents the effects of IL-1 through IL-6:
IL-1: promotes (hot) fever
IL-2: stimulates proliferation/differentiation of T cells
IL-3: stimulates proliferation of granulocytes and stem cells in the bone marrow
IL-4: stimulates class switching to IgE
IL-5: stimulates class switching to IgA
IL-6: stimulates the synthesis of aKute phase reactants
- 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 .
- 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|| |
|Interferon alpha (IFN-α)|| || |
|Interferon beta (IFN-β)|| |
|Interferon gamma (IFN-γ)|| || |
- Pro-inflammatory cytokines secreted by macrophages and leukocytes in response to inflammation and/or infection
- Their signaling pathways regulate inflammation, apoptosis, and cellular proliferation and differentiation.
- There are more than 20 tumor necrosis factors, of which TNF-α and TNF-β are the most important.
|Secreted by||Functions||Therapeutic use|
|Tumor necrosis factor alpha (TNF-α; cachectin)|| |
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.
- Eicosanoids are pro-inflammatory and anti-inflammatory autocrine or paracrine cell signaling molecules that are derived from arachidonic acid (AA).
- There are four subtypes of eicosanoids:
Arachidonic acid pathway
Phospholipase A2 breaks down cell membrane phospholipids to release AA.
- This step is inhibited by corticosteroids.
- AA is further metabolized in two major pathways:
- 5-lipoxygenase pathway
- Cyclooxygenase pathway
- The derivatives of these pathways are listed in the table below.
- Phospholipase A2 breaks down cell membrane phospholipids to release AA.
(analogs and inhibitors)
|Arachidonic acid|| |
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