Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

Read: How to Increase IL-10: An Anti-Inflammatory Cytokine That Leads to Weight Loss

In humans, IL-10 is produced by a variety of immune cells.  Since they're released by Th2 and Mast cells, they're part of the Th2 dominance category.  This is overly simplistic, however, because IL-10 also suppresses a Th2 response. (R)

IL-10 stimulates antibody production (by stimulating Plasma B Cells). (R, R2)  It can also stimulate a portion of CD8+ T-Cells and Natural Killer cells. (R)

The Good

We usually think of cytokines as "bad" and inflammatory.  IL-10 is an important exception. IL-10 is anti-inflammatory cytokine because it decreases various immune cells such as Th1 AND Th2 cells (R, R2),  neutrophils (R), macrophages and natural killer cells . (R)  The last three are the guns of the immune system. It also decreases a host of cytokines (IFNy, IL-2, TNF and GM-CSF) and other alarm bells of the immune system (MHCII). (R) It inhibits Nf-kB  (R) , the master control of inflammation (in,  two ways: by suppressing IKK activity and NF-ºB DNA binding (R)). It inhibits COX-2 (R), which is involved in migraines, pain and inflammation.  COX-2 is classically blocked by NSAIDs such as aspirin and ibuprofen. By inhibiting mast cells, it counteracts the inflammatory effect that these cells have at the site of an allergic reaction.  (R) IL-10 decreases obesity by reducing overeating and decreasing insulin and leptin resistance in the hypothalamus, the gland that control appetite (by inhibiting cytokines,  Nf-kB  and ER stress). (R) Higher IL-10 was associated with more white matter volume in visual areas and tracts (R)

IL-10 Creates 'Tolerance'

Perhaps most important function of IL-10 is its ability to help create 'tolerance' to the proteins we ingest and the proteins in our body.

IL-10 has been shown to increase Treg cells, which suppress undesired immune responses toward our selves, allergens and food proteins. (R) When we ingest a protein, the body has an elaborate mechanism by which to send the message to the immune system that this protein is cool and not harmful.  This is called "oral tolerance" - because we tolerate a protein that we ingest. IL-10  helps create oral tolerance, in addition to tolerance of our own body. (R)

The Bad

IL-10 can be considered good most of the time, but not all of the time. For example,  if we have an infection,  elevated IL-10 can block our ability to fight it effectively. In the modern era, this is usually good because because we can kill bacteria with the help of antibiotics and not rely solely on our immune system Genetic predisposition to high IL-10 is associated with a higher risk of death in meningitis. (R)

IL-10 Can Block Response to Viral Infections

By inhibiting the action of Natural Killer cells, IL-10 can also disrupt our ability to suppress viral infections. (R) Chronic viral infections can a source of cancer and autoimmune disease.

In fact, Epstein Barr Virus (EBV)/'Mono', Human Cytomegalovirus (HCMV) and some other viruses produce a molecule that's structurally similar to IL-10 in order to evade the immune system. (R, R2) (especially herpes family viruses (R))

Even more, IL-10 can directly increase production of viral proteins (R). IL-10 produced by these viruses stimulate antibody production more than regular IL-10 . (R) In Chronic Fatigue Syndrome, IL-10 is increased (R,R2), but it's not surprising.  

CFS is suspected to be from a viral infection and an inability to fight it.  IL-10 probably contributes to this. Chronically infected hepatitis C patients who are genetically predisposed to high IL-10 production had a less positive response to treatment and more likely to have problems after a transplant. (R)

IL-10 Can Promote Cancer

IL-10 also poses a problem when it comes to cancer. The Th1 immune system, specifically CD8+ T cells and IFNy, is part of the mechanism that we fight cancer.   Blocking IL-10 shows promise as a cancer treatment.  (R)

However, IL-10 also plays a protective anticancer role in some contexts by promoting cytotoxic T cell activity and IFN-³ production . (R)

It's important to realize that there's a difference between IL-10 levels systemically and in cancer tissue. If IL-10 is at healthy levels in normal tissue and low levels in cancerous tissue, then that's ideal, health wise.

The problem is that there's a correlation between systemic levels and levels in specific tissues. This is true for all tissues.  Blood levels of IL-10 are not necessarily indicative of levels in your gut or other tissues, but there's usually a correlation.  It's always most accurate to test the tissue itself, however.

IL-10 Can Contribute to Some Autoimmune Conditions

Since IL-10 increases antibody production, it can cause or worsen some autoimmune conditions. (R) So even though it's overall beneficial for inflammatory and autoimmune disorders, there are some exceptions.  See below.

The Bottom Line

In the modern environment, having high IL-10 levels is probably better than low IL-10 levels.  This is because we can fight bacterial infections and most viral infections don't cause us too much trouble, usually.

With regard to cancer, while it's true that high IL-10 levels can contribute to cancer, so can chronic inflammation (TNF, IL-1, IL-6, IL-17A).

For example, Th17/IL-17A is elevated in many cancers and promotes angiogenesis and stimulates proliferation+recruitment of neutrophils that can promote DNA damage through production of ROS/Free radicals.  

Their presence is associated with poor prognosis various cancers.  (R) IL-10 (and type I IFN) suppress Th17 inflammation and can, therefore, be anticancer in that respect. (R) Indeed, in some cancers, IL-10 can help kill tumors (R).

If we are suffering from issues that are associated with high or low IL-10 levels, then we should rebalance it with diet, lifestyle, and supplements.  And the solution will be different if you have high or low IL-10 levels.

The bottom line: IL-10 is a complex cytokine, but it's mostly good.  Obviously, having a balanced level is ideal.

Diseases Associated With Increased Levels

The most important thing to realize about IL-10 is that it responds to inflammatory states.  So as opposed to other cytokines, when it's elevated, it's more likely to be the case that you're already in an inflammatory state and the body is trying to bring the inflammation down.

• CFS (R,R2) - may help cause it
• Fibromyalgia (R)
• Migraines without aura (R) - less so in children (R)
• Schizophrenia (R)
• Atopic dermatitis (R), SLE (R), Systemic Sclerosis (R),
• Pancreatic cancer (R), Lymphoma, Melanoma (R),
• Heart disease (R) - IL-10 is protective against heart disease (R), but is likely elevated in response to inflammation.  So elevated IL-10 is just a signal that something's wrong, as far as science knows.

     From NCBI Gene: Human immunodeficiency virus type 1, susceptibility toRheumatoid arthritisGraft-versus-host disease, susceptibility to

     From NCBI Gene: The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis.[provided by RefSeq, May 2011] From UniProt: Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• Sp1
• STAT3
• C/EBPbeta
• NF-kappaB
• NF-kappaB1
• GR
• GR-alpha
• GR-beta
• AP-1
• IRF-1

Tissue specificity:

Produced by a variety of cell lines, including T-cells, macrophages, mast cells and other cell types.

Molecular Function:

• Cytokine Activity
• Interleukin-10 Receptor Binding
• Growth Factor Activity

Biological Processes:

• Response To Molecule Of Bacterial Origin
• Negative Regulation Of Cytokine Secretion Involved In Immune Response
• Negative Regulation Of Chronic Inflammatory Response To Antigenic Stimulus
• Positive Regulation Of B Cell Apoptotic Process
• Inflammatory Response
• Cytoplasmic Sequestering Of Nf-Kappab
• Cell-Cell Signaling
• Aging
• Negative Regulation Of Cell Proliferation
• Regulation Of Gene Expression
• Hemopoiesis
• B Cell Differentiation
• Leukocyte Chemotaxis
• Negative Regulation Of Myeloid Dendritic Cell Activation
• Negative Regulation Of B Cell Proliferation
• Negative Regulation Of Interferon-Gamma Production
• Negative Regulation Of Interleukin-1 Production
• Negative Regulation Of Interleukin-12 Production
• Negative Regulation Of Interleukin-18 Production
• Negative Regulation Of Interleukin-6 Production
• Negative Regulation Of Interleukin-8 Production
• Negative Regulation Of Tumor Necrosis Factor Production
• Receptor Biosynthetic Process
• Response To Insulin
• Negative Regulation Of Heterotypic Cell-Cell Adhesion
• Positive Regulation Of Heterotypic Cell-Cell Adhesion
• Response To Carbon Monoxide
• Cellular Response To Hepatocyte Growth Factor Stimulus
• Type 2 Immune Response
• B Cell Proliferation
• Negative Regulation Of T Cell Proliferation
• Negative Regulation Of Tumor Necrosis Factor Biosynthetic Process
• Defense Response To Bacterium
• Defense Response To Protozoan
• Positive Regulation Of Macrophage Activation
• Negative Regulation Of Apoptotic Process
• Negative Regulation Of Growth Of Symbiont In Host
• Negative Regulation Of Nitric Oxide Biosynthetic Process
• Regulation Of Isotype Switching
• Negative Regulation Of Mhc Class Ii Biosynthetic Process
• Positive Regulation Of Mhc Class Ii Biosynthetic Process
• Negative Regulation Of Interferon-Alpha Biosynthetic Process
• Positive Regulation Of Transcription, Dna-Templated
• Negative Regulation Of Mitotic Cell Cycle
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Positive Regulation Of Jak-Stat Cascade
• Positive Regulation Of Cytokine Secretion
• Regulation Of Synapse Organization
• Negative Regulation Of Membrane Protein Ectodomain Proteolysis
• Positive Regulation Of Sequence-Specific Dna Binding Transcription Factor Activity
• Response To Glucocorticoid
• Regulation Of Sensory Perception Of Pain
• Negative Regulation Of Cytokine Activity
• Branching Involved In Labyrinthine Layer Morphogenesis
• Cellular Response To Lipopolysaccharide
• Cellular Response To Estradiol Stimulus
• Negative Regulation Of Chemokine (C-C Motif) Ligand 5 Production
• Endothelial Cell Apoptotic Process
• Liver Regeneration
• Regulation Of Response To Wounding
• Negative Regulation Of Sensory Perception Of Pain
• Negative Regulation Of Vascular Smooth Muscle Cell Proliferation
• Positive Regulation Of Vascular Smooth Muscle Cell Proliferation

*synonyms