Immuno-stimulation, Immuno-modulation or what?

As pharmacology discovers the possibilities offered by the plant kingdom, it has found it necessary to coin new words to describe how the plants work. These definitions are an expression of normalizing, whole plant activity that cannot be covered by the semantics of reductionist, `active constituent’ research.

  • Immuno-stimulants or immuno-potentiators lead to a nonspecific stimulation of the immunological defense system. Nonspecific immuno-stimulants do not affect memory cells and since their pharmacological efficacy fades comparatively quickly, they have to be administered either in intervals or continuously. Protective immunity due to immuno-stimulants is brought about quickly and has been termed paramunity.
  • Immuno-modulation. However, these herbs may also stimulate T-suppresser cells and thereby reduce immune resistance. Therefore the terms immuno-modulationor immuno-regulation, denoting any effect on immune responsiveness, have been proposed.
  • Immuno-adjuvants are substances that enhance the production of antibodies without acting as antigens themselves. The effects of adjutants are often thymus-dependent.

The phytotherapist is quite at home with these `vague’ concepts, for after all, humanity is rarely governed by logic and rationale! This is explored later in this section. From the allopathic perspective, however, a number of therapeutic possibilities can be recognized as being offered by such `immuno-stimulation’. Whilst limited when seen in a phytotherapeutic context, they hint at the changes in perspective that are underway within orthodox medicine. The main areas are:

  • Immuno-stimulation potentially provides an alternative to conventional chemotherapy of infections, especially with patient’s having an impaired immune response. As it focuses on the bodies own immune mechanisms, there is the possibility of preventing opportunistic infections in patients at risk.
  • There is much that can be utilized in the therapy of malignant diseases. It is well known that tumor growth can be inhibited by stimulating specific components of the immune system, such as macrophages or T-killer cells.
  • Plant based immune stimulation may also contribute to the therapy of the autoimmune diseases.

Mechanism of Immuno-stimulation

As already discussed, immunological defense is a complicated interplay of many factors. The multifactorial nature of whole plant pharmacology compounds attempts by researchers to identify mechanism at work here. To simplify matters it is clear that irrespective of the primary targets of the immuno-stimulant, be they T or B lymphocytes or the complement system, an increase in phagocytosis by macrophages and granulocytes plays a central role in immuno-stimulation.

Molecules from the plant kingdom that impact the immune system

The more research that is done, the greater the range of plant species and constituents that seem to be involved. There is still far too little research to make generalizations, but far too often lack of research is taken to mean that the herb in question has no such properties. This is self-evidently absurd. The excellent studies being undertaken by Chinese and Japanese scientists on their traditional remedies is revealing much of importance to immunology. However, the same attention is rarely given to traditional European or North American herbs. This is because of research grants, not because of an inherent lack of value in the plants. Perhaps if Nettles (Urtica dioica) were given the same quality of attention that Astragalus has garnered for itself, we might have the immunological `proof’ of its profound effects.

In their comprehensive review, Wagner and Proksch have grouped the identified immuno-stimulatory constituents into high and low molecular weight compounds. Their groupings are :

Low molecular weight compounds

  • Alkaloids and other nitrogen containing compounds. A number of these have immunological activity of some kind. However the effects described by the umbrella term `immuno-modulation’ are often subtle, and on the whole bio-active alkaloids are definitely not subtle! Examples include aristolochic acid, from Serpentary (Aristolochia clematis); cepharanthinefrom Stephania cepharantha; tylophorine from Tylophoraindica.
  • Terpenes. Important sesquiterpene immuno-stimulants include helenalin, tenulin, eupahyssopin. This group of compounds abound in much of our materia medica. Research on Arnica montana suggests that theses quiterpenes component is pivotal to many of its actions. Many saponins, the more complex triterpenes, are considered to be `immuno-adjutants’ and are widely used as such in Japan, either in the form of the plant source or as the extracted chemical.
  • Phenols. A number of aromatic (in the chemical sense) molecule shave demonstrated immunological effects. The aromatic acids are ubiquitous amongst flowering plants, fruits and vegetables. Laboratory research has found that ferulic acid, named after Asafoetida (Ferula foetida), increases phagocytosis in mice; anethol, found in aniseed oil, increase the leucocyte count in the blood; the widely found pseudotannin catechol stimulates granulocytes. The more complex lignans are proving to be important, with a range of effects including stimulation of phagocytic activity inpolymorpho-nuclear granulocytes, cytotoxicity and induction of interferon.

High molecular weight compounds

These appear to be the most important immuno-stimulant plant constituents, especially the lectins (glycoproteins) and polysaccharides. It has been suggested that their impact is based upon some interaction with the membranes of `immuno-competent’ cells.

  • Lectins. Sugar binding, carbohydrate specific proteins that agglutinate some cells, such as the erythrocytes of certain blood types, and precipitate some molecules. Originally found in plants they were called phytohemagglutinins, however they have been found in bacteria, fungi, invertebrates, and most vertebrates. Some well known plant toxicity problems are due to lectins, e.g. ricin from Castor bean. A range of effects have been shown in the laboratory, including stimulation of mitosis in lymphocytes, inhibition of protein synthesis in bacteria, agglutination of malignant cells (tumor-specific lectins).Plants familiar to the herbalist that contain lectins are Phytolaccadecandra, Viscum album.
  • Polysaccharides. It is increasingly being suggested that the polysaccharide are at the core of herbal immuno-modulating effects. Laboratory studies have revealed a range of impressive results, including :

    • a general improvement of many immune response measures
    • T lymphocyte activation
    • anti-tumor activity
    • increase in certain serum proteins
    • non-specific activation of the complement system
    • stimulation of interferon production
    • stimulate increased phagocytosis

For species specific findings please see to the references given above, but as an example consider the following table. Sources are listed in Wagner and Proksch.

Influence of Polysaccharide fractions on Phagocytosis
Herb — enhancement of phagocytosis

Echinacea purpurea 45%

Eupatorium cannabinum 22%

Eupatorium perfoliatum 37%

Matricaria recutita 31%

Arnica montana 44%

Sabal serrulata 36%

Eleutherococcus senticosus 52%

Chemically undefined active plants

Some research has been done on whole plant extracts, but not in such a way that pointed to specific chemicals. In other words they looked at the stuff of Herbalism! As already pointed out, much of the research has been done with oriental plants, but a selective list of plants used in western Herbalism having a demonstrable impact on immune response might include :
Althaea officinalis

Arnica montana

Baptisia tinctoria

Bryonia dioica

Calendula officinalis

Echinacea angustifolia

Echinacea purpurea

Eleutherococcus senticosus

Eupatorium cannabinum

Eupatorium perfoliatum

Euphrasia officinalis

Gelsemium sempervirens

Glycyrrhiza glabra

Marrubium vulgare

Matricaria recutita

Peumus boldo

Phytolacca decandra

Sabal serrulata

Scrophularia nodosa

Thuja occidentalis

If there is a herb that interests you that is not on list, remember that lack of research does not mean the herb has no value.

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Written by David L. Hoffmann BSc Hons MNIMH

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