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Opioids as growth regulators of normal and malignant immunohaematopoesis - A review

Opioid peptides, originally known as neurotransmitters, participate in regulation of the immune response and affect cell proliferation. There are four families of opioid peptides: enkephalins, dynorphins, endomorphins and endorphins. They bind to respective receptors designated delta, kappa or mu. Synthetic opioids are more stable than the natural compounds. Recent evidence shows that cells of the immunohematopoetic system release natural opioids and express delta-, kappa- and mu- opioid receptors. Data about the effects of enkephalins on normal immunohematopoesis are contradictory. Enkephalins have been described to inhibit, stimulate or bidirectionally modulate cell proliferation in hematopoietic and lymphatic tissues. The release of cytokines may be inhibited, stimulated or modulated. Synthetic opioids usually inhibit normal immunohematopoesis and suppress cytokine release. Enkephalins and synthetic opioids have been described as negative regulators of malignant immunohematopoesis. Apoptosis has been considered a possible mechanism of action. Opioids also play a role in HIV infection. Synthetic delta and kappa-opioids inhibited the expresson of HIV in T-helper lymphocytes whereas mu-opioid morphine increased it. In short, actions of natural and synthetic opioids are not restricted to the nervous system, they affect normal and neoplastic cells in other tissues as well, including the lymphatic tissue and hematopoiesis. This pleiotropism is consistent with a holistic concept of the body.

opioids; haematopoiesis; immunity; lymphatic tissue; cytokines; HIV

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