---
title: "Inflammation Part 4: Cytokines & Their Functions"
description: "Inflammation: A focus on cytokines Part 2| optimaldx.com"
---

[The Optimal DX Research Blog ](https://www.optimaldx.com/research-blog)

# [Inflammation Part 4: Cytokines & Their Functions](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-2)

 Written by [ODX Research](https://www.optimaldx.com/research-blog/author/odx-research) | Jan 15, 2021 8:00:00 AM

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](https://www.optimaldx.com/research-blog/inflammation-part-1)
2. [Inflammation Part 2 - The Fire Inside - "Inflammaging"](https://www.optimaldx.com/research-blog/inflammation-part-2-inflammaging)
3. [Inflammation Part 3 - A Focus on Cytokines](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-1)
4. [Inflammation Part 4 - Cytokines & Their Functions](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-2)
5. [Inflammation Part 5 - The Cytokine Storm](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-3)
6. [Inflammation Part 6 - Cytokine Biomarkers](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-4)
7. [Inflammation Part 7 - Establishing Cytokine Ranges](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-5)
8. [Inflammation Part 8 - Interleukin 6](https://www.optimaldx.com/research-blog/inflammation-interleukin-6-and-10-part-1)
9. [Inflammation Part 9 - Interleukin 10](https://www.optimaldx.com/research-blog/inflammation-interleukin-6-and-10-part-2)
10. [Inflammation Part 10 - The IL-6 : IL-10 Ratio](https://www.optimaldx.com/research-blog/inflammation-interleukin-6-and-10-part-3)
11. [Inflammation Part 11 - Resolution & Intervention](https://www.optimaldx.com/research-blog/inflammation-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]](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-2?hs_amp=true#_edn1)

### **Sources of specific cytokines and their functions**[**[2]**](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-2?hs_amp=true#_edn2)

| **Cytokine** | **Family** | **Main sources** | **Function** |
| --- | --- | --- | --- |
| IL-1β | IL-1 | Macrophages, monocytes | Pro-inflammation, proliferation, apoptosis, differentiation |
| IL-4 | IL-4 | Th-cells | Anti-inflammation, T-cell and B-cell proliferation, B-cell differentiation |
| IL-6 | IL-6 | Macrophages, T-cells, adipocyte | Pro-inflammation, differentiation, cytokine production |
| IL-8 | CXC | Macrophages, epithelial cells, endothelial cells | Pro-inflammation, chemotaxis, angiogenesis |
| IL-10 | IL-10 | Monocytes, T-cells, B-cells | Anti-inflammation, inhibition of the pro-inflammatory cytokines |
| IL-12 | IL-12 | Dendritic cells, macrophages, neutrophils | Pro-inflammation, cell differentiation, activates NK cell |
| IL-11 | IL-6 | Fibroblasts, neurons, epithelial cells | Anti-inflammation, differentiation, induces acute phase protein |
| TNF-α | TNF | Macrophages, NK cells, CD4+lymphocytes, adipocyte | Pro-inflammation, cytokine production, cell proliferation, apoptosis, anti-infection |
| IFN-γ   | INF | T-cells, NK cells, NKT cells | Pro-inflammation, innate, adaptive immunity anti-viral |
| GM-CSF | IL-4 | T-cells, macrophages, fibroblasts   | Pro-inflammation, macrophage activation, increase neutrophil and monocyte function |
| TGF-β | TGF   | 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](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-3)

## Research

[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. 

[View full post](https://www.optimaldx.com/research-blog/inflammation-cytokines-part-2)

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