Glutathione and Immunity

November 29, 2020 //

Glutathione and Immunity – Important Roles in Correct Immune System Function

Immunity has two basic functions: to protect our body from threats coming from the outside, like bacteria or viruses, and to protect the body from its own damaged cells.

When the first one fails, we get sick with infectious disease. When the second one fails, we develop an autoimmune disease or cancer.

Glutathione plays an important role in both of these processes. In this article you will find out:

  • In what way is our immune system dependent on glutathione?
  • Which infectious or autoimmune diseases are connected with glutathione?
  • Which ones can be helped by supplementing glutathione or by modulating its metabolism?

Glutathione and Immune System Cells

It is widely accepted that GSH may play a critical role in the immune system.

In the human body everything is connected and all cells communicate with complex molecular signals, and the immune system is no different.

GSH is one of those molecular signals: when cells sense low levels of it, to them it means that the body is exhausted from something (be it infection, inflammation, injury, or simple stress) and the various immune cells go into power-saving mode: lymphocytes, macrophages and other immune system cells lower their activity which makes the organism more suspect to infections and inflammatory diseases.[1]

In many diseases, very low or completely depleted levels of GSH were reported, which points us towards the huge importance of GSH for a healthy life and prevention of diseases.[2]

Woman Coughing Due to Illness

Tuberculosis

Tuberculosis is the leading bacterial cause of death worldwide. It is a serious infection caused by a style-like bacteria Mycobacterium tuberculosis. In the developed world the disease is not as prevalent due to common vaccination and good treatment options for the infected individuals, but developing countries bear the burden of this disease. The most common form is the pulmonary tuberculosis which attacks the lungs, but there are other types as well (attacking central nervous system, lymph nodes, bones).

It has been proven that the patients suffering from acute lung tuberculosis have very low levels of glutathione in their white blood cells. This is a result of the acute infection – in an attempt to neutralize the bacteria and the inflammation in the lung tissue, white blood cells use their glutathione reserves to power their anti-inflammatory and antioxidant activity.

An additional reason to consider supplementing glutathione to tuberculosis patients is very peculiar: it appears to be toxic to Mycobacterium tuberculosis!

As a matter of fact, M. tuberculosis don’t use GSH in their cells at all, instead they have mycothiols for regulating their reduction or oxidation activities. And since they create infection by multiplying inside various cells (this is called ‘intracellular parasite‘), high concentrations of GSH in our cells might be beneficial for killing the Mycobacterium.[3] This is an experimental therapy undergoing clinical studies.

HIV and AIDS

According to the World Health Organization, a staggering 34 million people in the world are infected with HIV.

Since the first reported case in 1981, which started the epidemic, 25 million individuals have lost their lives to AIDS-related causes.

It is a viral disease caused by the HIV virus that attacks vital cells in the human immune system, such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells. Eventually, it renders the immune system so weak that the patients develop various opportunistic infections which are the actual cause of death.

3D depicition of a virus

Luckily, nowadays there are several options for the treatment of HIV with antiretroviral drugs. Recently, several studies reported that HIV+ patients have significantly lower GSH levels compared to healthy individuals; GSH levels are reduced to depletion in plasma, blood mononuclear cells and monocytes both in HIV-infected individuals and in AIDS patients, and this deficiency seems to correlate with disease morbidity.

When glutathione is depleted in lung cells of HIV patients, there is a higher predisposition to opportunistic infections that interestingly can be repleted using aerosolised GSH. Also the cachexia and wasting syndrome of AIDS may be due to GSH depletion.

When we consider the major role of GSH in the immune system, antioxidant activity and cell signaling, it seems like a very natural conclusion and several studies already started to experiment with GSH as an adjuvant therapy for HIV+ patients.[1],[2]

Inflammatory diseases of the digestive system

Several clinical conditions, especially inflammatory/immunomediated disorders, have been associated not only with oxidative stress, but also with damaged antioxidant status due to the reduced GSH levels.

For example, in patients with Crohn’s disease (a painful chronic inflammation of the bowels), in the affected ileal zones there were very low GSH levels and GSH-related enzymes were altered.

This is a typical occurrence for many other chronic inflammatory diseases, because the prolonged and repeated inflammation causes the depletion of your body’s protective systems.[2]

Inflammatory Bowel Disease

Probiotic bacteria such as lactobacilli possess strong antioxidant potential. Inflammatory diseases in the gut such as inflammatory bowel disease, Crohn’s disease, and ulcerative colitis may be positively influenced by the antioxidant activity of resident intestinal bacteria.

Some specific strains of lactobacilli have an increased level of GSH peroxidase enzyme, which is a promising new lead in probiotic therapy.

This enzyme not only helps the bacteria to survive in the gut, but also benefits the host through the increased antioxidant activity. This might help alleviate the inflammation in the above-mentioned chronic conditions.[2]

Cancer

Numerous factors contribute to the initiation, development and progression of cancer including those of genetic, environmental and dietary influences. Glutathione and GSH-metabolism participate in different ways in cancer prevention and progression. Many studies have shown the role of UV radiation exposure, chemical carcinogens, environmental agents, inflammation and diet, in cancer etiology.

By its antioxidant properties, GSH participates in the defense against carcinogens by protecting cells from DNA-damage and harmful oxidation of cell systems.

Unfortunately, it is not as simple as “if I take GSH every day, I won’t get cancer“.

Some cancer cells actually develop increased GSH production to increase their chemotherapy resistance. When antineoplastic or chemotherapeutic drugs enter these cancer cells, they are conjugated with glutathione and are excreted through GSH pumps before they have a chance to kill the cell. Therefore in cancer patients, all medications have to be carefully selected based on the precise type of the cancer cells they are targeting.

DNA Strand

GSH metabolism-targeting drugs might be a new type of therapy to reduce chemotherapy resistance.[4]

Many potential treatments that can interfere with the GSH system in solid tumors have been shown to have anti-tumor effects both in test tubes and in living organisms, but only a few clinical trials with these compounds have been completed.

The clinical trials that have been conducted to date have reported promising effects against solid tumors, mainly when combined with traditional chemotherapeutic drugs. However, some clinical trials have not yet reported their results.

Preclinical studies that target the GSH system in cancer cells date back to the 1980‘s, but only a few compounds have come to market as antineoplastic drugs. This is for several reasons:

  1. The GSH system is present in several cells and partially responsible for the cell’s defense against reactive species. Nonselective compounds that target the GSH system may produce significant alterations of redox control in healthy cells and produce more damage than benefit. Nanoparticles that specifically target cancer cells are an interesting option, but only a few such studies have been conducted.
  2. Clinical trials that exclusively evaluate compounds that affect the GSH system have not yet been conducted.
  3. Tumor cells are rapidly tuned to the tumor microenvironment and are able to react very quickly to drugs. After drug removal, GSH is rapidly resynthesized in these cancer cells.

Based on the preclinical data, patients with leukemia and solid tumors of the ovaries, liver, colon, and lungs may see the most benefit from chemotherapeutic agents that target the GSH system.[5]

Summary: Glutathione and Immune Function

Glutathione is an important compound for the immune system of human body. Not only does it maintain the antioxidative balance, but also helps the immune system cells in their activities. It is an essential compound in fighting the bacterial and viral pathogens, as well as the damaged cells of our own bodies. It modulates inflammation and healing process.

Low levels of GSH are associated with infections, autoimmune and inflammatory diseases and cancer and usually signalize the exhausted immune and antioxidant system. In several diagnoses, therapy with GSH supplements is already undergoing studies and trials, the most hopeful being HIV/AIDS and chemotherapy-resistant cancer.

The take-home message for your everyday life would be to live a healthy lifestyle with enough building blocks for your body to create enough glutathione, or with occasional glutathione supplements (more on that in this article – Benefits of Glutathione Injections). This might assure that your immune system cells are well-stocked on glutathione and prepared to protect your body from everything harmful.

Further Reading:


References:

[1] Kelly and Pearce. Amino Assets: How Amino Acids Support Immunity. Cell Metabolism 32 (2020).

[2] C. Perricone et al. Glutathione: A key player in autoimmunity. Autoimmunity Reviews 8 (2009) 697–701

[3] D. Morris, et al., Glutathione and infection. Biochim. Biophys. Acta 2012.

[4] R. Franco et al. The central role of glutathione in the pathophysiology of human diseases. Archives of Physiology and Biochemistry 2007; 113(4/5), 234 – 258

[5] C.R. Corso, A. Acco. Glutathione system in animal model of solid tumors: From regulation to therapeutic target. Critical Reviews in Oncology / Hematology 128 (2018) 43–57