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CYTOKINES & AUTOIMMUNITY

Cytokines are tiny proteins released by cells to modify the role of the same or another cell.  They include interleukins, chemokines, interferons, adipokines and others.  They are chemical intracellular messengers and are found sizably in the immune system to help initiate and control the immune response.  They bind to specific receptors on the cell surface of target cells and switch on the intracellular signalling cascade via complex interactions.   Cytokines are key modulators of acute and chronic inflammation.  Dysregulation of cytokine production or action is thought to have a key role in the development of  Autoimmune diseases.

Cytokines

The Complex Cytokine Network

All Immune cells have distinct roles and communicate with other cells via cytokines. For example, Macrophages can use cytokines to stimulate specific  responses by B and T cells and non-specific responses by other cell types. T cells secrete cytokines to coordinate and stimulate immune responses to specific antigens. Activation and modulation of eosinophils, neutrophils and basophils are also via cytokines.


Reference: (Zhang, Jun-Ming MSc, MD*; An, Jianxiong, 2007)

doi: https://dx.doi.org/10.1097%2FAIA.0b013e318034194e

Types of Cytokines

Pro-inflammatory cytokines and Anti-inflammatory cytokines are the two types of cytokines that exist.

Pro-inflammatory cytokines (eg. IL-1beta, IL6, TNF-alpha) activate the immune and cytokine response.   

Anti-inflammatory cytokines (eg. IL-4, IL-10, IL-11, IL-13, TGF-Beta) regulate the pro-inflammatory cytokines. 

Reference: (Rabaan, Ali A et al. 2021)  

doi:10.3390/vaccines9050436

Types of Cytokines
A cytokine storm

A Cytokine Storm

An effective immune response requires a balance between sufficient cytokine production to eliminate a threat and avoidance of a hyperinflammatory, overblown and dysregulated response in which an overabundance of cytokines may cause tissue damage. The term “cytokine storm” is an abrupt upregulation of cytokines provoking the inflammatory process, resulting in high levels of circulating cytokines and immune-cell hyperactivation.  A cytokine storm can be triggered by pathogens, cancers and Autoimmune conditions.

Reference: (David C. Fajgenbaum, and Carl H. June, 2020)

DOI: 10.1056/NEJMra2026131

Cytokines in Autoimmunity

Autoimmune diseases are often associated with disturbances in the  balance between immunoregulatory  and proinflammatory cytokines and the persistent overproduction of inflammatory cytokines.  High levels of IFN-g, IL-17, IL-21, and IL-6 cytokines have all been linked with various Autoimmune diseases.

The emergence of successful biological therapies targeting cytokines and cytokine receptors highlights the role of cytokines in the pathogenesis of Autoimmunity and also provides hope for new therapeutic opportunities. 

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