Study 16
Modulation of cytokine expression by hypericum extract
AU: Thiele-B; Brink-I; Ploch-M
AD: Medizinische Fakultat (Charite) der Humboldt Universitat zu Berlin, Germany.
SO: J-Geriatr-Psychiatry-Neurol. 1994 Oct; 7 Suppl 1: S60-2
Introduction
Recent research suggests that except for the well known role of neurotransmitters like serotonin and norepinephrine, there might also be other important physiological mechanisms involved in the patophysiology of depression.
One of these is the possible indirect actions via the immune system.
The immune system and the nervous system are the only known biological structures possessing a memory capacity.
How these memory functions actually work is still largely unknown, but we know that there is a lot of interaction between the CNS and the immune system. Part of this is due to production and secretion of certain molecules, including endorphins, ACTH (adreno-cortico-trope hormone), ADH (anti-diuretical hormone) and in particular certain cytokines. Cytokines are heavily involved in the communication between cells inside and outside the immune system, especially in the nervous system. Virtually all systematic manifestations of immune system activation are mediated either directly or indirectly by the brain or the endocrine organs. Activation of the immune system is causally associated with extensive changes in neural and/or endocrine functions.
These changes include fever, somnolence, loss of appetite, activation of the hypothalamic-hypophyseal-adrenal axis and suppression of the hypothalamic-hypophyseal-gonadal axis and that of the hypothalamic-hypophyseal-thyroid.
It cannot be ruled out that, in subjects with an appropriate disposition, monocyteinterleukins (monokines) are capable of inducing all the signs of depressive illness. According to this hypothesis, a large variety of white blood mononuclear cells (stimulated by infection, allergy, estrogen) would lead to increased levels of interleukins, resulting in changes in mental state.
The aim of this pilot study was to determine whether hypericum extract LI 160 exerts effects on the immune system in vitro, compatible with the "mediator theory" of its antidepressant effect.
Description
The effect of hypericum extract LI 160 on the stimulated cytokine expression was investigated in vitro in a whole blood culture system on non-immune-stimulated cells and on cells stimulated by phytohemagglutinin (PHA) or lipopolysaccharides (LPS). Blood samples were taken from five healthy volunteers and four depressive patients.
The release of the cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) was measured quantitatively after an incubation time of 24 hours on microtiter plates.
The hypericin concentration was 2 microl/200 microl = 10 microl/ml = 10mg/ml =120 000 ng/ml hypericin.
Steady state concentration of hypericin during treatment with hypericin was measured to 5 ng/ml by Staffeldt et al.
Results
Researchers' comments
Cytokines affect the nervous system both directly and indirectly.
IL-1 had the following direct effects:
IL-1B and IL-6 have the following effects:
Other facts:
Hypericum appears to reduce the interleukin-6 excretion, which in turn reduces the CRH, ACTH and corticosteroid secretion.
Copyright © 1996 by Harold H. Bloomfield, M.D. and Peter McWilliams
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