MLT and the immune-hematopoietic system.

It is now well recognized that a main actor in the continuous interaction between the nervous and immune systems is the pineal hormone MLT. T-helper cells bear G-protein coupled MLT cell membrane receptors and, perhaps, MLT nuclear receptors. Activation of MLT receptors enhances the release of T-helper cell type 1 (Th1) cytokines, such as gamma-interferon and interleukin-2 (IL-2), as well as of novel opioid cytokines which crossreact immunologically with both interleukin-4 (IL-4) and dynorphin B. MLT has been reported also to enhance the production of interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-12 (IL-12) in human monocytes. These mediators may counteract stress-induced immunodepression and other secondary immunodeficiencies, protect mice against lethal viral and bacterial diseases, synergize with IL-2 in cancer patients and influence hematopoiesis. In cancer patients, MLT seems to be required for the effectiveness of low dose IL-2 in those neoplasias that are generally resistant to IL-2 alone. Hematopoiesis is apparently influenced by the action of the MLT-induced-opioids (MIO) on kappa-opioid receptors present on stromal bone marrow macrophages. Most interestingly, gamma-interferon and colony stimulating factors (CSFs) may modulate the production of MLT in the pineal gland. A hypothetical pineal-immune-hematopoietic network is, therefore, taking shape. From the immunopharmacological and ethical point of view, clinical studies on the effect of MLT in combination with IL-2 or other cytokines in viral disease including human immunodeficiency virus-infected patients and cancer patients are needed. In conclusion, MLT seems to play a crucial role in the homeostatic interactions between the brain and the immune-hematopoietic system and deserves to be further studied to identify its therapeutic indications and its adverse effects.