Research Blog

January 15, 2021

Inflammation Part 4: Cytokines & Their Functions

Welcome to part 4 of the ODX Inflammation Series. In this post, the ODX Research Team reviews cytokines, their sources and their functions.

Sources of Cytokines and their Function

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

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.[1]

Sources of specific cytokines and their functions[2]



Main sources




Macrophages, monocytes

Pro-inflammation, proliferation, apoptosis, differentiation




Anti-inflammation, T-cell and B-cell proliferation, B-cell differentiation



Macrophages, T-cells, adipocyte

Pro-inflammation, differentiation, cytokine production



Macrophages, epithelial cells, endothelial cells

Pro-inflammation, chemotaxis, angiogenesis



Monocytes, T-cells, B-cells

Anti-inflammation, inhibition of the pro-inflammatory cytokines



Dendritic cells, macrophages, neutrophils

Pro-inflammation, cell differentiation, activates NK cell



Fibroblasts, neurons, epithelial cells

Anti-inflammation, differentiation, induces acute phase protein



Macrophages, NK cells, CD4+lymphocytes, adipocyte

Pro-inflammation, cytokine production, cell proliferation, apoptosis, anti-infection




T-cells, NK cells, NKT cells

Pro-inflammation, innate, adaptive immunity anti-viral



T-cells, macrophages, fibroblasts


Pro-inflammation, macrophage activation, increase neutrophil and monocyte function




Macrophages, T cells

Anti-inflammation, inhibition of pro-inflammatory cytokine production


Clinical significance of select cytokines: [3]

Interleukin-1 (IL-1)


Macrophages, large granular lymphocytes, B cells, endothelium, fibroblasts, and astrocytes secrete IL-1. T cells, B cells, macrophages, endothelium and tissue cells are the principal targets. IL-1 causes lymphocyte activation, macrophage stimulation, increased leukocyte/endothelial adhesion, fever due to hypothalamus stimulation, and release of acute phase proteins by the liver. It may also cause apoptosis in many cell types and cachexia.

IL-1 acts on the hypothalamus to induce fever and is therefore called an endogenous pyrogen. It operates on hepatocytes to increase synthesis of specific serum proteins, such as amyloid A protein and fibrinogen. It causes fall in blood pressure or shock in large amounts. Corticosteroids inhibit the IL-1 effect.

Interleukin-2 (IL-2)


T cells produce IL-2. The principal targets are T cells. Its primary effects are T-cell proliferation and differentiation, increased cytokine synthesis, potentiating Fas-mediated apoptosis, and promoting regulatory T cell development. It causes proliferation and activation of NK cells and B-cell proliferation and antibody synthesis. Also, it stimulates the activation of cytotoxic lymphocytes and macrophages

Gene knockout mouse studies have provided evidence that the primary IL-2 function in vivo is the suppression of T responses. Mice lacking IL-2 or its receptor (CD25) develop lymphadenopathy and T cell-mediated autoimmunity.

Interleukin-3 (IL-3)

T cells and stem cells make IL-3. It functions as a multilineage colony-stimulating factor.

Interleukin-4 (IL-4)


CD4+T cells (Th2) synthesize IL-4, and it acts on both B and T cells. It is a B-cell growth factor and causes IgE and IgG1 isotype selection. It causes Th2 differentiation and proliferation, and it inhibits IFN gamma-mediated activation on macrophages. It promotes mast cell proliferation in vivo.

Interleukin-5 (IL-5)


CD4+T cells (Th2) produce IL-5, and its principal targets are B cells. It causes B-cell growth factor and differentiation and IgA selection. Besides, causes eosinophil activation and increased production of these innate immune cells.

Interleukin-6 (IL-6)


T and B lymphocytes, fibroblasts and macrophages make IL-6. B lymphocytes and hepatocytes are its principal targets. IL-6 primary effects include B-cell differentiation and stimulation of acute phase proteins.

Interleukin-7 (IL-7)

Bone marrow stromal cells produce IL-7 that acts on pre-B cells and T cells. It causes B-cell and T-cell proliferation.

Interleukin-8 (IL-8)


Monocytes and fibroblasts make IL-8. Its principal targets are neutrophils, basophils, mast cells, macrophages, and keratinocytes. It causes neutrophil chemotaxis, angiogenesis, superoxide release, and granule release.

Interleukin-9 (IL-9)  

Th9, Th2, Th17, mast cells, NKT cells, and regulatory T cells produce this cytokine. It enhances T-cell survival, mast cell activation and synergy with erythropoietin.

Interleukin-10 (IL-10)


Th2 cells produce IL-10. Its principal targets are Th1 cells. It causes inhibition of IL-2 and interferon gamma. It decreases the antigen presentation, and MHC class II expression of dendritic cells, co-stimulatory molecules on macrophages and it also downregulates pathogenic Th17 cell responses. It inhibits IL-12 production by macrophages.

Knockout mice lacking IL-10 develop inflammatory bowel disease, probably because of uncontrolled activation of macrophages reacting to enteric microbes. 

Interleukin-11 (IL-11)


Bone marrow stromal cells and fibroblasts produce IL-11. The IL-11 principal targets are hemopoietic progenitors and osteoclasts. The IL-11 primary effects include osteoclast formation, colony stimulating factor, raised platelet count in vivo, and inhibition of pro-inflammatory cytokine production.

Interleukin-12 (IL-12)


Monocytes produce IL-12. Its principal targets are T cells. It causes induction of Th1 cells. Besides, it is a potent inducer of interferon gamma production by T lymphocytes and NK cells.

IL-12 overproduction causes allergic disorders. Corticosteroids inhibit the effects of IL-12.

Interleukin-13 (IL-13)


CD4+T cells (Th2), NKT cells and mast cells synthesize IL-13. It acts on monocytes, fibroblasts, epithelial cells and B cells. The IL-13 significant effects are B-cell growth and differentiation, stimulates isotype switching to IgE. It causes increased mucus production by epithelial cells, increased collagen synthesis by fibroblasts and inhibits pro-inflammatory cytokine production. Also, IL-13 works together with IL-4 in producing biologic effects associated with allergic inflammation and in defense against parasites.

Interleukin-14 (IL-14)

T cells produce IL-14, and its principal effects are stimulation of activated B cell proliferation and inhibition of immunoglobulin secretion.

Interleukin-15 (IL-15)


Monocytes, epithelium, and muscles make IL-15. It acts on T cells and activated B cells. It causes the proliferation of both B and T cells. It causes NK cell memory and CD8+ T cell proliferation.

Interleukin-16 (IL-16)

Eosinophils and CD8+T cells synthesize IL-16. Its principal target is CD4+ T cells. It causes CD4+ T cell chemoattraction.

Interleukin-17 (IL-17)


This cytokine is produced by Th-17. It acts on epithelial and endothelial cells. IL-17 main effects are the release of IL-6 and other pro-inflammatory cytokines. It enhances the activities of antigen-presenting cells. It stimulates chemokine synthesis by endothelial cells.

Interleukin-18 (IL-18)

Macrophages mostly make IL-18, which can be produced by hepatocytes and keratinocytes. Its principal target is a co-factor in Th1 cell induction. It causes interferon gamma production and enhances NK cell activity.

Interleukin-19 (IL-19)


Th2 lymphocytes synthesize IL-19 and acts on resident vascular cells in addition to immune cells. It is an anti-inflammatory molecule. It promotes immune responses mediated by regulatory lymphocytes and has substantial activity on microvascular.

IL-19 may be used to induce angiogenesis in ischemic tissue.

Interleukin-20 (IL-20)


Immune cells and activated epithelial cells secrete IL-20. It acts on epithelial cells. It plays a vital role in the cellular communication between epithelial cells and the immune system under inflammatory conditions.

Interleukin-21 (IL-21)


NK cells and CD4+ T lymphocytes make IL-21. It acts on various immune cells of innate and the adaptive immune systems. IL-21 promotes B and T lymphocyte proliferation and differentiation. It enhances NK cell activity.

The administration of IL-21 may be considered for use as a preventive and therapeutic approach when dealing with Th2-mediated allergic diseases.

Interleukin-22 (IL-22)


Different cells in both innate and acquired immunities produce IL-22, but the primary sources are T cells. Th22 cell is a new line of CD4+ T cells, which differentiated from naive T cells in the presence of various pro-inflammatory cytokines including IL-6. IL-22 inhibits IL-4 production. It also has essential functions in mucosal surface protection and tissue repair.

Interleukin-23 (IL-23)

Macrophages and dendritic cells mainly synthesize IL-23. It acts on T cells causing maintenance of IL-17 producing T cells.

Interleukin-24 (IL-24)


Monocytes, T and B cells mostly make IL-24. It causes cancer-specific cell death, causes wound healing and protects against bacterial infections and cardiovascular diseases.

Interleukin-25 (IL-25)

Dendritic cells produced predominantly IL-25. It acts on various types of cells, including Th2 cells. It stimulates the synthesis of Th2 cytokine profile including IL-4 and IL-13.

Interleukin-26 (IL-26)


It is strongly associated inflammatory activity with IL-26. Th17 cells produce this interleukin. It acts on epithelial cells and intestinal epithelial cells. It induces IL-10 expression, stimulates the production of IL-1-beta, IL-6, and IL-8 and causes Th17 cell generation.

IL-26 shows high expression in psoriatic skin lesions, colonic lesions from individuals with inflammatory bowel disease and synovia of individuals with rheumatoid arthritis. It may constitute a promising target to treat chronic inflammatory disorders.

Interleukin-27 (IL-27)


T cells make IL-27 that activates STAT-1 and STAT-3, which regulates immune responses. IL-27 stimulates IL-10 production. It is a pro-inflammatory molecule and upregulates type-2 interferon synthesis by natural killer cells.

IL-27 was found to exerts anti-inflammatory effects in several experimental autoimmune models. IL-27 treatment suppressed autoimmune diabetes.  

Interleukin-28 (IL-28)


Regulatory T-cells synthesize IL-28, which acts on keratinocytes and melanocytes. It stimulates cell presentation of viral antigens to CD8+T lymphocytes. IL-28 also upregulates TLR-2 and TLR-3 expression. IL-28 enhances the keratinocyte capacity to recognize pathogens in the healthy skin.

IL-28 may be sufficient treatment of HCV patients.

Interleukin-29 (IL-29)


IL-29 is a type-3 interferon and produced by virus-infected cells, dendritic cells, and regulatory T-cells. It upregulates viral protective responses. Virus-infected cells may regulate IL-29 genome.

IL-29 is a marker of osteoarthritis as joint inflammation implicates it.

Interleukin-30 (IL-30)


Monocytes mainly produce IL-30 in response to TLR agonists including bacterial LPS. It acts on monocytes, macrophages, dendritic cells, T and B lymphocytes, natural killer cells, mast cells, and endothelial cells.

Interleukin-31 (IL-31)


IL-31 is produced mainly by Th2 cells and dendritic cells. It is a proinflammatory cytokine and a chemotactic factor that direct polymorphonuclear cells, monocytes, and T cells to inflammatory lesions. IL-31 induces chemokines production and synthesis of IL-6, IL-16, and IL-32.

Interleukin-32 (IL-32)


IL-32 is a pro-inflammatory molecule. Natural killer cells and monocytes mainly produce it. IL-32 induces the synthesis of various cytokines including IL-6, and IL-1beta. It inhibits IL-15 production.

Interleukin-33 (IL-33)


Mast cells and Th2 lymphocytes express IL-33 that acts on various innate and immune cells including dendritic cells and T and B lymphocytes. It mediates Th2 responses and therefore participates in the protection against parasites and type-I hypersensitivity reaction.

Interleukin-34 (IL-34)


Various phagocytes and epithelial cells synthesize Interleukin-34 (IL-34). It enhances IL-6 production and participates in the differentiation and development of antigen-presenting cells including microglia.

Interleukin-35 (IL-35)

Regulatory B cells mainly secrete it. One of the primary functions of this interleukin is its involvement in lymphocyte differentiation. It exhibits an immune-suppressive effect.

Interleukin-36 (IL-36)


Phagocytes mainly make IL-36. It acts on T lymphocytes and NK cells regulating the IFN-γ synthesis. It stimulates the hematopoiesis and expression of both MHC class I and II molecules as well as intracellular adhesion molecules (ICAM)-1.  

IL-36 also seems to play a significant role in human psoriasis. In psoriatic lesion tissues, IL-36 levels were found to be elevated, and generalized pustular psoriasis was also discovered, which is rare and life-threatening. 

Interleukin-37 (IL-37)


IL-37 plays an essential role in the regulation of the innate immunity causing immunosuppression. Phagocytes and organs including the uterus, testis, and thymus express it.

IL-37 upregulates immune responses and inflammation in autoimmune disorders.

In lupus patients were elevated IL-37 levels in comparison with healthy controls, and mucocutaneous and renal involvement was correlated with high disease activity.

Interleukin-38 (IL-38)

Il-38 acts on T cells and inhibits the synthesis of IL-17 and IL-22.  The placenta, tonsil's B lymphocytes, spleen, skin, and thymus widely express IL-38.

Recent studies point to an association between IL-38 and autoimmune diseases. Its role in carcinogenesis or cancer growth is unclear.  

Interleukin (IL-39)


B lymphocytes mainly produce IL-39. It acts on neutrophils inducing their differentiation or expansion.

IL-39 secreted by activated B cells may be a critical pro-inflammatory cytokine and a potential therapeutic target for the treatment of autoimmune diseases such as systemic lupus erythematosus.

Interleukin-40 (IL-40)


IL-40 is produced in the bone marrow, fetal liver, and by activated B cells. IL-40 plays a vital role in the development of humoral immune responses.

IL-40 expression in several human B-cell lymphomas suggests that it may play a role in the pathogenesis of these diseases.

Ultimately, cytokines are complex in that they can be produced by and have effects on a variety of tissues. They can have pro- and anti-inflammatory effects; can work together to upregulate or downregulate other cytokines, and some may exert both pro- and anti-inflammatory effects depending on signaling pathways: [4]

Next Up: Inflammation Part 5 - The Cytokine Storm


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

[2] Chen, Linlin et al. “Inflammatory responses and inflammation-associated diseases in organs.” Oncotarget vol. 9,6 7204-7218. 14 Dec. 2017. 

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

[4] Monastero, Rebecca N, and Srinivas Pentyala. “Cytokines as Biomarkers and Their Respective Clinical Cutoff Levels.” International journal of inflammation vol. 2017 (2017): 4309485. 

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