ScienceDaily (May 9, 2008) — Infection with human immunodeficiency virus (HIV), which leads to acquired immunodeficiency syndrome (AIDS), is an epidemic of global concern. According to the most recent estimates, released in November 2007, by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO), an estimated 33.2 million worldwide are living with HIV infection currently. Although the rates of infection appear to be decreasing, there are obviously immense implications for achieving improvements in HIV/AIDS treatment.

The functioning of natural killer (NK) cells, which are a major element of the innate immunity system and are involved in the body’s first line of defense against infections such as HIV, is decreased in both HIV and depression. A group of researchers who have previously found that stress and depression impair NK cell function and accelerate the course of HIV/AIDS are now publishing a new report in Biological Psychiatry.

In this study, they recruited both depressed and non-depressed HIV-infected women and studied the ex vivo effects of three drugs, a selective serotonin reuptake inhibitor (SSRI), a substance P antagonist, and a glucocorticoid antagonist, on their NK cell activity. These drugs were selected because, as the authors state, each “affect[s] underlying regulatory systems that have been extensively investigated in both stress and depression research as well as immune and viral research.”

The scientists found that the SSRI citalopram, and the substance P antagonist CP 96,345, but not the glucocorticoid receptor antagonist RU486, increased NK cell activity. According to Dr. Dwight Evans, corresponding author of the article: “The present findings provide evidence that natural killer cell function in HIV infection may be enhanced by selective serotonin reuptake inhibition and also by substance P antagonism in both depressed and non-depressed individuals.”

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments: “There has been growing evidence that the compromise of immune function associated with depression influences the outcomes of infectious diseases and cancer. Antidepressant treatments are beginning to be studied for their potential positive effects on immune function.”

He adds that “the paper by Evans et al. suggests that antidepressant treatment may have positive effects on natural killer cell activity in cells isolated from individuals infected with HIV with and without depression. This type of bridge between the brain and the rest of the body deserves further attention.” Dr. Evans agrees, noting that “these findings begin to pave the way towards initiating clinical studies addressing the potential role of serotonergic agents and substance P antagonists in improving natural killer cell innate immunity, possibly delaying HIV disease progression and extending survival with HIV infection.”

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Journal reference:

1. Selective Serotonin Reuptake Inhibitor and Substance P Antagonist Enhancement of Natural Killer Cell Innate Immunity in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome. Dwight L. Evans, Kevin G. Lynch, Tami Benton, Benoit Dubé, David R. Gettes, Nancy B. Tustin, Jian Ping Lai, David Metzger and Steven D. Douglas. Drs. Evans, Lynch, Benton, Dubé, and Metzger and Mr. Gettes are affiliated with the Department of Psychiatry, with Dr. Evans also with the Departments of Medicine and Neuroscience, and Dr. Douglas is with the Department of Pediatrics, all at the University of Pennsylvania School of Medicine in Philadelphia, Pennsylvania. Ms. Tustin and Drs. Lai and Douglas are with the Division of Allergy and Immunology, Joseph J. Stokes Research Institute of The Children’s Hospital of Philadelphia, in Philadelphia, Pennsylvania. Biological Psychiatry, Volume 63, Issue 9 (May 1, 2008).

Adapted from materials provided by Elsevier, via EurekAlert!, a service of AAAS.

Written by Dr. James Meschino, D.C., M.S.,
– Research and Clinical Director, RenaiSanté Institute of Integrative Medicine –

Recent And Historical Use Of Reishi Mushroom Extract
Reishi mushroom (Ganoderma lucidum) is called “the mushroom of immortality” in China and has been used in Oriental Medicine for over 2,000 years. ^(1,2) In recent years its active ingredients have been the subject of intensive research regarding their apparent ability to help prevent or treat certain types of cancer, aid in the treatment of liver disease, HIV infection, acute or recurrent herpetic infections, high blood pressure, chronic bronchitis, allergies and asthma, and favorably modulate immune function. ⁽³⁾ The reishi mushroom grows wild on decaying logs and tree stumps in the coastal provinces of China. The fruiting body of the mushroom is used medicinally. ⁽⁴⁾

Active Constituents: Reishi mushrooms contain a number of active agents that are known to modulate function of the immune system in humans. The primary agents include:

1. Specific Polysaccharides - which occur in the form of Beta-D-glucans bound to amino acids. These agents are known to possess immune-modulating and anti-cancer properties. (3)
2. Triterpene compounds - known as ganoderic acids, which have been shown to lower blood pressure, reduce platelet stickiness and may decrease LDL-cholesterol. (5)
3. Other major active constituents - including sterols, coumarin and mannitol. (5)

Clinical Application and Mechanism of Action

1. Anti-Cancer Agent: Cancer studies in animals have shown a 50% tumor regression rate with reishi mushroom extract treatment (e.g., connective tissue cancer model in mice). ⁽⁶⁾ Reishi mushroom extract is used by some cancer surgeons in Japan to treat cancer patients and significant anti-tumor and immunostimulation effects have been noted in many of these cases. ⁽⁷⁾ Polysaccharides from reishi mushrooms and from other types of folk-medicinal fungi are patented in Japan for use as immunomodulators in the treatment of cancer. They are combined with chemo- and radiotherapy and have demonstrated an ability to reduce side effects, increase the efficacy of treatments, and are used to accelerate recovery from disease. ^(8,9)
   Studies from China have shown that reishi mushroom extract potentiates the tumoricidal capacity of macrophages and T-cells. ^(10,11) Reishi mushroom extract is known to have other immune modulating effects and antioxidant properties as well. ^{(12,13,14,15,16)}
2. Immune System Enhancement: (Bronchitis, Asthma, Allergies, Herpetic Conditions and HIV Infection) As noted above, reishi mushroom extract modulates many components of the immune system, which in part, account for its apparent anti-tumor properties. Chronic bronchitis in the elderly has been shown to respond favorably to treatment using a concentrated reishi mushroom product in a trial involving 2,000 cases in China. This study demonstrated a better than 60% success rate. After several months of treatment there was a noted rise in the levels of immunoglobulin A in the sputum. ⁽¹⁰
   The combination of astragalus and reishi mushroom extract represents an effective means of daily immune support and a therapeutic intervention for a large number of immune compromised states (e.g.,chronic fatigue, chronic bronchitis, herpes I and II recurrent infections, post-herpetic neuralgia, recurrent apthous ulcers or canker sores, the common cold, HIV infection, etc.) and for patients undergoing chemo-or radiation therapy.
3. Cardiovascular Health: (High Blood Pressure and Reduced Platelet Aggregation) Two human controlled studies revealed that reishi mushroom extract can reduce high blood pressure to a significant degree (systolic and diastolic), even in patients who had previously failed to respond to established anti-hypertensive medications. ^(30,31) Animal studies reveal that reishi mushroom extract reduces blood pressure through a central inhibition of sympathetic nerve activity, although it does not slow heart rate or induce a sedative effect in general. ⁽³²
4. Liver Protective Effects: (Hepatoprotective Properties) Reishi is prescribed in China for the treatment of chronic and acute hepatitis. ⁽³⁶⁾ Various ganoderic acids in reishi mushrooms have strong antihepatotoxic properties, ⁽³⁷⁾ which under experimental conditions have been shown to protect liver cells from chemically-induced injury, including protection from the highly toxic and lethal substance, carbon tetrachloride. ^(38,39)

ScienceDaily (Aug. 15, 2005) — Monash University scientists have rejuvenated the immune systems of mice and humans using a common hormone.

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The scientists, led by Associate Professor Richard Boyd and Dr Jayne Sutherland from the Monash Immunology and Stem Cell Laboratories, have revitalised the thymus which produces the T cells required to fight infection but which shuts down from early adulthood.Their achievement, published in the August issue of the Journal of Immunology, has offered new hope for patients with cancer, AIDS and other immunodeficiencies and for transplant patients.

The Monash study showed inhibiting sex steroids through the Leuteinizing Hormone-Releasing Hormone could help regrow the thymus, increase output of new T cells, enhance T cell responses and improve recovery following bone marrow transplants. It also showed, for the first time, that prostate cancer patients who had their sex steroids temporarily blocked had increased levels of new T cells in their blood.

The researchers found inhibiting sex steroids improved the production of haemopoietic stem cells in bone marrow. These cells provide ‘fuel’ for the bone marrow and thymus to produce blood cells.

Associate Professor Boyd said the immune system deteriorated severely with age, and was further destroyed by severe viral infection and common cancer treatments such as chemotherapy and radiotherapy.

“The resulting immunodeficiency can allow cancer relapse and leave patients at greater risk of infections which are often fatal,” he said. “The ability to overcome these immune system deficiencies provides a completely new approach to treating cancer and may work in many other severe clinical conditions such as HIV/AIDS. It may also boost the effectiveness of vaccines to cancer and infections.”

Because the scientists have been able to manipulate the way the thymus grows back, they believe they should be able to rebuild the immune system of patients who are receiving transplants so donor material is not rejected.

The group has initiated pre-clinical trials using this technology to induce immune tolerance to organ transplants. The trials, led by clinical immunologist Dr David Sachs, are being undertaken at the Massachusetts General Hospital, the largest teaching affiliate of Harvard Medical School.

The technology, licensed to Norwood Immunology, is also about to be used in clinical trials in leading US cancer centres on patients receiving chemotherapy and haemopoietic stem cell transplants.

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Adapted from materials provided by Research Australia, via EurekAlert!, a service of AAAS.