Inflammation Part 3: A focus on cytokines

Inflammation: A Focus on Cytokines 

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

The ODX Inflammation Series

1. Inflammation Part 1 - The Fire Inside - Overview
2. Inflammation Part 2 - The Fire Inside - "Inflammaging"
3. Inflammation Part 3 - A Focus on Cytokines
4. Inflammation Part 4 - Cytokines & Their Functions
5. Inflammation Part 5 - The Cytokine Storm
6. Inflammation Part 6 - Cytokine Biomarkers
7. Inflammation Part 7 - Establishing Cytokine Ranges
8. Inflammation Part 8 - Interleukin 6
9. Inflammation Part 9 - Interleukin 10
10. Inflammation Part 10 - The IL-6 : IL-10 Ratio
11. Inflammation Part 11 - Resolution & Intervention

Cytokines are basically messengers that facilitate immune function and take part in pro-inflammatory, anti-inflammatory, and allergic responses. [1]

They can have an effect on the cells that produce them (autocrine action), cells close to them (paracrine action), or cells further away (endocrine action).

• Cytokines may be named for the cells that produce them or their actions. For example,
  • Monokines (produced by monocytes)
  • Lymphokines (produced by lymphocytes)
  • Chemokines have chemotactic action
  • Interleukins are produced by one leukocyte with an effect on another leukocyte

However, there is overlap where one cytokine may perform several functions, or functions may change depending on target cells. Also, the presence or absence of other cytokines may determine a cytokine’s effects. [2]

For example, interleukin-6, IL-1, TNF-alpha (cachectin), TNF-beta, and interferon-alpha overlap in their physiological actions. [3]

A wide variety of cells produce cytokines, including fibroblasts, nerve, mast, glial, adipose, and endothelial cells, though macrophages and helper T (Th) lymphocytes are the primary producers.[4]

Helper T cells express CD4 cell surface molecules and are divided into Th1 and Th2 and therefore produce Th1 and Th2-type cytokines which must strike a dynamic balance in order to maintain homeostasis: [5]

Th1 cytokines

• Primarily pro-inflammatory
• Kill off intracellular parasites
• Promote autoimmune reactions
• Interferon gamma is a primary Th1 cytokine

Th2 cytokines

• Balance Th1 immune response
• Promote IgE and eosinophil allergic reactions (IL-4, IL-5, IL-13)
• Can be anti-inflammatory (IL-10)
• Excess Th2 cytokines may inhibit Th1 antimicrobial action
• Th2 reduce risk of miscarriage by modifying Th1 response in utero

In general, Th1 cells facilitate cell-mediated immunity and Th2 cells facilitate humoral and allergic responses. [6]

Interleukins are produced by a range of cells, not by leukocytes alone. They retain both autocrine and paracrine actions; possess anti- and pro-inflammatory effects; stimulate immune cell differentiation; and can have redundant functions. For example, B-cell differentiation is promoted by IL-4, IL-5, and IL-13. [7]

Cytokines may affect metabolism by increasing amino acid uptake and protein synthesis in the liver, promoting muscle breakdown, and stimulating gluconeogenesis. Excess cytokine production may be tempered by the vagus nerve via a cholinergic anti-inflammatory pathway. [8]

Next Up: Inflammation Part 4 - Cytokines and Their Function

Research

[1] Berger, Abi. "Th1 and Th2 responses: what are they?." Bmj 321.7258 (2000): 424.

[2] Tisoncik, Jennifer R et al. “Into the eye of the cytokine storm.” Microbiology and molecular biology reviews : MMBR vol. 76,1 (2012): 16-32. 

[3] Mahan, L. Kathleen; Raymond, Janice L. Krause's Food & the Nutrition Care Process - E-Book (Krause's Food & Nutrition Therapy). Elsevier Health Sciences. Kindle Edition.

[4] Zhang, Jun-Ming, and Jianxiong An. “Cytokines, inflammation, and pain.” International anesthesiology clinics vol. 45,2 (2007): 27-37. 

[5] Berger, Abi. "Th1 and Th2 responses: what are they?." Bmj 321.7258 (2000): 424. 

[6] Chaplin, David D. “Overview of the immune response.” The Journal of allergy and clinical immunology vol. 125,2 Suppl 2 (2010): S3-23. 

[7] Justiz Vaillant, Angel A. and Ahmad Qurie. “Interleukin.” StatPearls, StatPearls Publishing, 30 August 2020. 

[8] Mahan, L. Kathleen; Raymond, Janice L. Krause's Food & the Nutrition Care Process - E-Book (Krause's Food & Nutrition Therapy). Elsevier Health Sciences. Kindle Edition.