Cytokines

Immunology

See Also

• Interleukins
• Cell mediated immunity
• Natural Killer (NK) Cells
• T lymphocyte
• Transcription factors

Description

Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. They must be produced de novo in response to an immune stimulus. They generally (although not always) act over short distances and short time spans and at very low concentration. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior (gene expression). Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation, and secretion of effector molecules.

Non-nutrient environmental factors affecting cytokine concentration

From Kaput and Rodriguez (1)

• Overall sleep time and sleep continuity
• Oxygen tension, which is related to altitude.
• Over-the-counter drugs (e.g., nonsteroidal anti-inflammatory drugs)
• Water intake relative to tea and other beverages.
• Physical activity, including genetic fitness to activity
• Psychological factors like stress
• Exposure to allergens and pollutants
• Circadian rhythm and seasonal changes
• Balance between energy intake and expenditure

Discussion

Cytokine blocking has had some clinical applications, including the use of Etanercept, a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human p75 TNF-alpha cellular receptor linked to the Fc portion of human immunoglobulin (Ig)G1 for the treament of Alzheimer's dementia. Etanercept specifically binds to TNF-alpha, rendering it biologically ineffective.(2)

Remicade (infliximab), also a TNF-alpha agonist, has been shown to have effectiveness in a variety of inflammatory conditions, including rheumatoid arthritis, ulcerative colitis and psoriasis. (3)

Cytokine activity decreases over time in stored blood. (4)

There is an expanding body of clinical and experimental evidence that cytokines, especially interleukin-1, tumor necrosis factor, interleukin-6, and interleukin-8, are principle mediators of immune responses to erythrocyte incompatibility. Recent studies have further suggested that the monocyte chemotactic and activating factor, monocyte chemoattractant protein-1, and the anti-inflammatory cytokine interleukin-1 receptor antagonist are produced in experimental models of hemolytic transfusion reactions. Differing levels and patterns of expression of these cytokines may be seen in models of intravascular hemolysis due to ABO incompatibility and extravascular hemolysis due to Rh incompatibility, which correlate with the recognized clinical differences between these two types of reactions. (5)

Selected Immune Cytokines and Their Activities
Cytokine	ProducingCell	TargetCell	Function**
GM-CSF	Th cells	progenitor cells	growth and differentiation of monocytes and DC
IL-1 alpha, IL-1 beta	monocytes macrophages B cells DC	Th cells	co-stimulation
		B cells	maturation and proliferation
		NK cells	activation
		various	inflammation, acute phase response, fever
IL-2	Th1 cells	activated T and B cells, NK cells	growth, proliferation, activation
IL-3	Th cells NK cells	stem cells	growth and differentiation
		mast cells	growth and histamine release
IL-4	Th2 cells	activated B cells	proliferation and differentiationIgG1 and IgE synthesis
		macrophages	MHC Class II
		T cells	proliferation
IL-5	Th2 cells	activated B cells	proliferation and differentiation, IgA synthesis
IL-6	monocytes macrophages Th2 cells stromal cells	activated B cells	differentiation into plasma cells
		plasma cells	antibody secretion
		stem cells	differentiation
		various	acute phase response
IL-7	marrow stroma thymus stroma	stem cells	differentiation into progenitor B and T cells
IL-8	macrophages endothelial cells	neutrophils	chemotaxis
IL-10	Th2 cells	macrophages	cytokine production
		B cells	activation
IL-12	macrophages B cells	activated Tc cells	differentiation into CTL(with IL-2)
		NK cells	activation
IFN- alpha	leukocytes	various	viral replicationMHC I expression
IFN- beta	fibroblasts	various	viral replication MHC I expression
IFN- gamma	Th1 cells, Tc cells, NK cells	various	Viral replication
		macrophages	MHC expression
		activated B cells	Ig class switch to IgG2a
		Th2 cells	proliferation
		macrophages	pathogen elimination
MIP-1 alpha	macrophages	monocytes, T cells	chemotaxis
MIP-1 beta	lymphocytes	monocytes, T cells	chemotaxis
TGF-beta	T cells, monocytes	monocytes, macrophages	chemotaxis
		activated macrophages	IL-1 synthesis
		activated B cells	IgA synthesis
		various	proliferation
TNF alpha	macrophages, mast cells, NK cells	macrophages	CAM and cytokines expression
		tumor cells	cell death
TNF- beta	Th1 and Tc cells	phagocytes	phagocytosis, NO production
		tumor cells	cell death

Links

• Cytokines

References