- 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., , , multiple sclerosis).
- 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-4 (IL-4)|| |
|Interleukin-11 (IL-11)|| |
|Interleukin-12 (IL-12)|| |
|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)
- 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
COX-1/COX-2 break down AA to release prostaglandin H2.
- This step is inhibited by (irreversible inhibition), other (reversible inhibition), and .
- COX-1/COX-2 break down AA to release prostaglandin H2.
- 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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