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).
Eicosanoids are proinflammatory and anti-inflammatory signaling molecules derived from arachidonic acid (AA) and include prostaglandins, leukotrienes, prostacyclins, and thromboxane A2. inteferon gamma (IFN gamma)
- proteins that are secreted mainly by immune cells (especially T lymphocytes) in response to a stimulus such as infection, ischemia, or injury. are small extracellular signaling
- Act on receptors to modulate immune responses, inflammation, and hematopoietic cellular proliferation and differentiation.
- Target receptor can be located on:
- Interleukins: cytokines secreted by a leukocyte that acts on another type of leukocyte
- Lymphokines: cytokines secreted by lymphocytes
- Monokines: cytokines secreted by monocytes
- Chemokines: cytokines that have chemotactic activities
Proinflammatory cytokines (Th1 cytokines): stimulate the immune system
- Interleukins 1, 6, 8, 12, 18, IFN-γ, and tumor necrosis factor (TNF)
- Induce fever, inflammation, and tissue destruction in response to infection, injury, or ischemia
- Cytokine storm: an excessive release of proinflammatory cytokines that causes hyperactivation of immune system and exaggerated immune response leading to
- Anti-inflammatory cytokines (Th2 cytokines): suppress the immune system
- 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.
|Overview of interleukins|
|Interleukin||Secreted by|| |
Targets and effect
|Interleukin-1 (IL-1)|| |
|Interleukin-2 (IL-2) |
|Interleukin-3 (IL-3)|| || |
|Interleukin-4 (IL-4) |
|Interleukin-6 (IL-6)|| |
|Interleukin-7 (IL-7)|| |
|Interleukin-8 (IL-8)|| |
|Interleukin-10 (IL-10)|| |
|Interleukin-11 (IL-11)|| |
|Interleukin-12 (IL-12)|| |
|Interleukin-17 (IL-17)|| |
|Interleukin-24 (IL-24)|| || |
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|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)
- 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
AMBOSS mnemonics 4 BEGinners help 2 put their mind at ease — Interleukin-4 stimulates growth of B cells, enables class switching to IgE and IgG and triggers T cell differentiation into Th2 (helper) cells.
IL-10 and TGF-β are both anTi-ENflammatory.
- Interferons are cell signaling glycoproteins 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.
- Have antiviral (RNA as well as DNA viruses); , antimicrobial, and antiproliferative properties
- Are a part of the
- 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) 
|Overview of interferons|
|Interferon||Mainly secreted by||Function|| |
|Side effects |
|Type I||Interferon alpha (IFN-α)|| |
|Interferon beta (IFN-β)|| |
|Type II||Interferon gamma (IFN-γ)|| || |
Interferons interfere with cells with an altered genetic interface (virus-infected and malignant ones).
Tumor necrosis factor superfamily 
- Pro-inflammatory cytokines secreted by leukocytes in response to inflammation and/or infection
- Their signaling pathways regulate inflammation, apoptosis, and cellular proliferation and differentiation.
- There are over 20 tumor necrosis factors, of which cachectin and lymphotoxin-alpha are the most important.
|Members of the tumor necrosis factor superfamily|
|Protein||Mainly secreted by||Functions||Therapeutic significance|
|Cachectin (tumor necrosis factor; formerly tumor necrosis factor-alpha)|| || |
- A group of regulatory proteins with similar structure and target receptors that are involved in:
- Dysregulation of TGF genes is implicated in the pathogenesis of autoimmune diseases and various types of cancers.
|Transforming growth factor family|
|Transforming growth factor-β (TGF-β) |
|Bone morphogenetic proteins || |
IL-10 and TGF-β are both anTi-ENflammatory.
- Eicosanoids are pro-inflammatory and anti-inflammatory autocrine or paracrine cell signaling molecules that are derived from arachidonic acid (ARA).
- Arachidonic acid
- There are four subtypes of eicosanoids:
Arachidonic acid pathway
AA is further metabolized in two major pathways, derivatives of which are shown in the table below.
- 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 .
|Derivatives of arachidonic pathway|
Clinical relevance (analogs and inhibitors)
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