Immune Stimulants

Use of Immune Stimulants to prevent viral reactivation

Most HHV-6 reactivation occurs in patients who are immunosuppressed, such as those undergoing stem cell transplantation or who have a genetic immune deficiency. In addition, some individuals may unknowingly become immunosuppressed in response to environmental or biochemical factors such as increased stress. Certain drugs and environmental toxins can activate HHV-6 virus, and several conditions involving extreme drug hypersensitivity reaction are accompanied by HHV-6 viremia (See HHV-6 & Drug Hypersensitivity.) Furthermore, once reactivated, HHV-6A and HHV-6B (as well as several other herpesviruses) can enhance this state of immunosuppression, leading to more rapid development of virus-related symptoms, persistent infection, and increased risk of reactivation and co-infection with other pathogens (See HHV-6 & Immune Suppression).

Patients with signs of viral reactivation (elevated titers or viremia) and frequent bouts of illness should ask their physicians about ruling out specific immune deficiencies. Here are some of the tests your primary care physician may order to rule out immune deficiencies:

Total IgG with subclasses
Lymphocyte Subset Panel (measures CD4, CD8, NK cells, etc)
ImmuKnow or Immune Cell Function test (measures CD4 response)
Natural Killer Cell Function

If any of these markers are abnormal, an immunologist should be consulted for a more detailed workup. For example, patients with low total IgG or a low value on one of the subclasses might be diagnosed with hypogammaglobulinemia or be treated with gammaglobulin shots or infusions to help maintain proper immune system health.

In addition, marked deficiencies in certain minerals such as zinc, magnesium and selenium are known to affect immune system functionality and limit immune response to viral infection. For this reason, the following tests are also suggested by many experts to rule out high-risk mineral deficiencies:

RBC magnesium
Zinc
Selenium

There are a few prescription drugs and nutraceuticals that may help stimulate immune response. We have listed a few of these below for information purposes only. Of course, you should always consult your physician before introducing any of these compounds into your own treatment regimen.

Prescription Drugs that Enhance Cellular Immune Response

Nexavir or Hepapressin (previously Kutapressin)

Nexco Pharmaceuticals has introduced a generic form of kutapressin, called Nexavir, which is based on the original formula consisting of processed extract from porcine livers that contain peptides with immune stimulating effects. Kutapressin has demonstrated efficacy against HHV-6 in a 1994 in-vitro study (Ablashi, Berneman et al. 1994) as it inhibited replication by over 90% and has also been used in the treatment of patients with herpes zoster. Results of uncontrolled studies have indicated that treatment with kutapressin results in the abatement of symptoms among many patients with CFS. Kutapressin has also improved the NK cell function in CFS patients. There have been no published studies on Nexavir so it is unknown if this treatment works as well as the original formula. Derek Enlander, MD often incorporates Hepapressin, similar to Kutapressin, into treatment regimens for patients with CFS.

Inosine Acedoben Dimepranol (IAD)

Also known by trade names such as Isoprinosine® Imunovir® Viruxan® Virimun® and Delimmun®, IAD is manufactured and supplied by Newport Pharmaceuticals Ltd, a small pharmaceutical company that is part of the larger Swiss-based Ewopharma Group. manufactures and supplies the API Inosine Acedoben Dimepranol (IAD) to Partners Worldwide. IAD is an immunomodulator that has been indicated for the treatment of cell mediated immune deficiencies associated with various viral infections.

Nutraceuticals with immune stimulating properties

Active Hexose Correlated Compound (AHCC)

This natural compound is made by culturing the mycelia of Basidiomycetes (mushrooms) via a patented process, and is widely used across Asia and in the US by cancer patients. It has been found in a number of studies to have immune simulating effects, and has been evaluated for safety in human trials of healthy volunteers and cancer patients (Terakawa 2008). A study in Japan showed that it increases dendritic cells in healthy volunteers and studies at Yale showed that AHCC increased the number of NK and gammadelta T cells, and enhanced CD4(+) and CD8(+) T immune responses for up to 30 days, suggesting that AHCC can regulate both the innate and adaptive immune responses (Yin 2010). In addition, a study among patients with liver cancer published in the Journal of Hepatology showed that AHCC significantly lowered the recurrence rate of liver cancer and increased survival (Gao 2006). A Phase 1 safety study was completed and demonstrated only mild and transient side effects using a dose higher than what would be anticipated for clinical use (Spierings 2007).

Fermented wheat germ extract (FWGE; Avemar)

This patented fermented wheat germ product is used as a nutritonal supplement for cancer patients. A number of papers have noted that FWGE induces apoptosis and stimulates NK cell activity, and enhances TNF secretion of the macrophages (Boros 2005, Mueller 2011, Mueller 2011b, Telekes 2009). The compound was developed in Hungary by scientists who followed up on the observation of Nobel prize winner Albert Szent-Gyorgyi who theorized that methoxy-substituted benzoquinones could help the body respond to external stresses. They developed a process to ferment wheat germ with baker’s yeast and the resulting compound is now used as an immune stimulator and to prevent metastasis in cancer. It has a strong impact on cellular immunity but no apparent impact on humoral response. Safety studies have shown that it has no evidence of mutagenicity or genotoxicity in vitro or in vivo (Heimbach 2007).

Whey protein concentrate (ImmunoPro)

Marketed by Well Wisdom in San Diego, CA, this product is a combination of undenatured whey, lactoferrin, active peptides, transfer factors and immunoglobulins from bovine colostrum. Bovine lactoferrin has immunomodulating, anti-microbial and anti-inflammatory properties (Madureira 2010). Lactoferrin has potent antiviral properties against HIV and CMV in vitro, and led to a 10-fold reduction of CMV levels after 4 weeks in one animal model study (Harmsen 1995, Beljaars 2004). Low molecular weight fraction bovine colostrum has been shown to increase the phagocytic activity of monocytes and increase the number of T cells and natural killer cells, and result in enhanced microbial clearance in animal infection models (Jensen 2012, Benson 2012). Immunopro/whey protein contains high levels of cysteine and other amino acids that are precursors to glutathione. Lymphocytes depend on high levels of glutathione for proper function and low levels of glutathione are associated with impaired T cell function poor survival in AIDS patients (Garaci 1992, De Rosa 2000). Whey protein has also been shown to enhance humoral immune response to vaccines in the elderly (Freeman 2010).

Foscarnet prophylaxis improved engraftment and survival in cord blood transplant patients

Latent HHV-6B infection of astrocytes may increase the risk of depression by activating the HPA axis

Mothers with iciHHV6 have an increased risk of spontaneous abortion

Significantly worse outcomes in critically ill hematology patients associated with HHV-6 infection.

Use of Immune Stimulants to prevent viral reactivation

Prescription Drugs that Enhance Cellular Immune Response

Nutraceuticals with immune stimulating properties