Immunostimulants

 Fig.1 Gram positive bacteria
Immunostimulants are boosters of the immune system that help with the body’s resistance to cope with viral and bacterial infections. Their aim is to help bacterial killing at the primary focus of infection, “to prevent the development of nosocomial infections and to prevent the reactivation of dormant viruses”1. This immunostimulants can also be used to help with the treatment of immunosupressed patients as in the case of AIDS and SARS.


The origin of immunostimulants are varied. They can be found in bacteria, nutritional supplements or could be synthesized for immunotherapy, as in the case of levamisole, an antineoplastic medication.

Polybacterial immunostimulants are mostly used to treat or prevent infection of the respiratory and urinary system. They are composed of gram-positive and gram-negative bacterial bodies and freeze-dried lysates. The gram-negative bacteria contain LPS endotoxins and lipoproteins that stimulate macrophages, NK cells, B-lymphocytes, production of antibodies and release of α and γ-interferon, IL-2 and IL-6. Gram-positive bacteria contain muramildipeptide, lipotheichoic acids and peptidoglycans, which also stimulate phagocytosis, T-cell and B-cell function.


Some examples are Respivax, Urostim and Dentavax. Respivax is composed of freeze-dried lysate and killed bacteria utilized to treat non-specific infections of the respiratory system, tonsillitis and pharyngitis. Urostim, also with freeze-dried lysate, is utilized to treat acute recurrent or chronic non-specific infections of the urinary tract in children and adults, such as cystitis and bateriuna. Dentavax it’s used to treat inflammatory and infectious diseases of the oral cavity2.


Another bacterial lysate treatment is Broncho-Vaxom (OM-85), used in patients with recurrent exacerbations of chronic bronchitis or mild chronic obstructive pulmonary disease (COPD). It stimulates the upregulation of secretory antibodies and activation of alveolar macrophages to influence the immune and inflammatory responses of the respiratory system. Clinical trials have demonstrated that in the setting of chronic bronchitis and mild-to-moderate COPD, OM-85 seems to protect against bronchitic exacerbations on these patients3.


A new study by Ohio State University suggests that antibody-based cancer drugs might be more effective if they are given in conjunction with immunostimulants4. For example, the drug trastuzumab may work better when it’s followed by injections of IL-2 or IL-12; substances that trigger the activity of NK cells. The combination of antibody-coated cells and IL-2 or IL-12 causes the NK cells to release substances that attract more potent immune cells, mainly killer T cells, thereby trigging a larger and more effective immune response against the tumor.
The vaccine against tuberculosis, BCG, made from attenuated Mycobacterium tuberculosis, has been used as an immunostimulant for the treatment of bladder cancer. Instillation directly into the bladder induces a variety of cytokines into the urine of patients of these patients. In addition, it may induce a cytokine-mediated antiangiogenic environment that aids in inhibiting future tumor growth and progression.5


Other potent immunostimulants are Beta-carotene and Echinacea in the form of nutritional supplements. They enhance cytokine-synthesizing capacity of macrophages; increase the number of T-helper cells and stimulates NK-cell activity. These complements must be used in addition to a balanced diet to prevent the toxic effects of over supplementation.6



Discussion Questions:


1. What are the major enviromental and Physiological problems facing immunostimulants today?

2. What does immunostimulants do and what factors of the immune system are stimulated by immunotherapy?

3. Which are the factors determining the interest to use the immunostimuants in the control of different infectious diseases?


Multiple Choice Questions:

1. Immunotherapy has a mechanism of action different from that of chemotherapy. It uses materials made by your own body or made in a laboratory to boost, direct, or restore your body's natural defenses against the tumor. What imunostimulant, commonly used for other diseases is used to treat transitional cell carcinoma?

A) Respivax
B) OM-85
C) BCG vaccine
D) Eccinacea

2. Hector recently developed a septic shock that altered his innate and adaptive immune responses leading to an impaired clearance of microorganism. What treatment will be beneficial to this patient?

A) Immunostimulants
B) Immunosuppressors
C) Radioactive immunotherapy
D) Protibiotics



3. Immunostimulants yield all of the following factors of the immune system EXCEPT:

a) phagocytosis
b) alpha and Beta interferon release
c) T and B Lymphocytes
d) protective secretory Ig M antibodies


References


1. Pugin J. Immunostimulation is a rational therapeutic strategy in sepsis. Novartis Found Symp. 2007 ; 280 :21-7; discussion 27-36. Available from: http://lib.bioinfo.pl/pmid:17380786. Accessed May 19, 2008.

2. Petrunov B, Nenkov P & Shekerdjiisky. The Role of Immunostimulants in Immunotherapy and Immunoprophylaxis.Biotechnol & Biotechnol .2007. 454 -463 http://www.diagnosisp.com/dp/journals/
view_pdf.php?journal_id=1&archive=1&issue_id=16&article_id=443&PHPSESSID=634532481
140d5ec4065231691d74d51 Accessed May 19, 2008

3. Soler M. Modulation of airway inflammation to prevent exacerbations of COPD. European Respiratory Review, 2005;14: 78-82. Available from: http://err.ersjournals.com/cgi/content/full/14/95/78#R21. Accessed May 19, 2008

4. Brown CK, Kirkwood JM. Immunotherapy of Cancer. Hor Cancer Therapeutics. 2001; 2(1): 3-23. Available from: http://www.meniscus.com/horizons/2-1.pdf. Accessed May 19, 2008

5. Bladder Cancer Web Café. BCG page. Available at: http://blcwebcafe.org/bcg.asp. Accesed May 21, 2008

6. Gleeson M. Nutritional Supplements For Sport – Immunostimulants. Available at: http://www.medicdirectsport.com/sportsnutrition/default.asp?step=4&pid=437. Accessed May 21, 2008