Neuroimmunomodulation – A Scientific Foundation for an Ancient Skill

Dr R Saso
Royal Marsden Hospital, London, England

The immune system represents a multisystem comprised of components derived from central nervous (CNS), endocrine (ES) and immune system (IS).1 A term neuroimmunomodulation (NIM) was coined to describe the permanent intercommunication between these systems. They exchange information on the basis of shared receptors and biochemical substances.2 By modulation of their production it is possible to affect the function of the immune system. The immunointervention could be achieved by direct influence on the immune system or indirectly by modulating activity of the CNS or Endocrine System (ES).

A lot of evidence has been accumulated over last several years on the underlying pathophysiological mechanism of the acupuncture.3 Stimulation of different acupoints could produce a certain amount of neurotransmitters, neuromodulators, neurohormones and cytokines.4 They can either directly affect the components of the immune system or indirectly by activating the neuroendocrine axis. The main neuroimmunomodulators released after acupuncture stimulation are opioid peptides: the enkephalins, endorphins and dynorphins.5;6 The experimental results suggest a bi-modal, dose dependent effect of the opioid peptides on the immune system, met-enkephalin (Met-Enk) and leu-enkephalin (Leu-Enk) being the most extensively studied opioid peptides.7

It is now clear that Met-Enk and Leu-Enk are not equipotent since the former has been more active in modulating the immune response. Met-Enk injected peripherally in high doses suppresses, whereas in low doses enhances, immune reactions. Injection of Met-Enk into the cerebral cavity (ICV) of the rat sensitised with bovine albumin could modulate cutaneous delayed hypersensitivity to the antigen more effectively than when injected peripherally. So, delayed cutaneous reactions were increased after small dose intraventricular injection of Met-Enk, whereas the large dose of the same enkephalin induced decreased skin reactions.8;9

At a certain dose Met-Enk could be a potent anti-inflammatory agent, or may even prevent anaphylactic shock.10

Enkephalins are able to prolong survival time of mice inoculated with tumour cells. In vivo treatment of cancer patients could also result in immunomodulation. Of great interest are the results that showed, in vitro as well as in vivo, that the enkephalins can enhance NK and T cell activity. Therefore by increasing activity of NK cells it would be possible to enhance host resistance to viral and tumour challenge.11

The rapidly expanding area of NIM has become an unlimited source of data that has enabled us to understand and scientifically explain the ancient skill of acupuncture.

Reference list

1. Jankovic BD. The immune microenvironment is a multisystem. Immunol Lett 1979;1:145-6.

2. Blalock JE. Production of peptide hormones and neurotransmitters by the immune system. Chem Immunol 1992;521-24.

3. Bossy J. Immune systems, defense mechanisms and acupuncture: Fundamental and practical aspects. Am J Acupunct 1990;18(3):219-32.

4. Lundeberg T, Eriksson SV, Theodorsson E. Neuroimmunomodulatory effects of acupuncture in mice. Neurosci Lett 1991;128(2):161-4.

5. Fujiwara R, Tong ZG, Matsuoka H, Shibata H, Iwamoto M, Yokoyama MM. Effects of acupuncture on immune response in mice. Int J Neurosci 1991;57(1-2):141-50.

6. Sakic B, Kojic L, Jankovic BD, Skokljev A. Electro-acupuncture modifies humoral immune response in the rat. Acupunct Electrother Res 1989;14(2):115-20.

7. Jankovic BD. Neuroimmunomodulation: From phenomenology to molecular evidence. Ann NY Acad Sci 1994;741:1-38.

8. Jankovic BD, Maric D. Enkephalins and immunity. I: In vivo suppression and potentiation of humoral immune response. Ann NY Acad Sci 1987;496:115-25.

9. Maric D, Jankovic BD. Enkephalins and immunity. II: In vivo modulation of cell-mediated immunity. Ann NY Acad Sci 1987;496:126-36.

10. Jankovic BD, Maric D. Enkephalins and anaphylactic shock: Modulation and prevention of shock in the rat. Immunol Lett 1987;15:153-60.

11. Plotnikoff NP. Opioids: immunomodulators. A proposed role in cancer and aging. Ann NY Acad Sci 1988;521:312-22.

Biographical Note

Dr Saso was born, educated and medically trained in Greater Yugoslavia. He completed his postgraduate studies in the Immunology Research Centre, University of Belgrade. He did some studies in neuroimmunology including some early work on the influence of acupuncture on immune response. Later on he completed his training in internal medicine and haematology. He spent a year as a British Council Scholar at St Thomas' Hospital and RPMS at Hammersmith. He studied the role of different lymphokines in antigen presentation and T-lymphocyte proliferation. After obtaining his doctorate (PhD) he was promoted to Assistant Professor in Internal Medicine/Haematology in 1991 at the University of Saints Cyril & Methodius, Skopje. In 1992 he returned to the UK and continued his work in haematology at St George's Hospital and later on at the Royal Marsden Hospital. He is currently working in the Haemato-Oncology Unit of the Royal Marsden Hospital. Dr Saso's long-term interest is in haemato-oncology and bone marrow transplantation.

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