Interleukin-1 beta and thymic peptide regulation of pituitary and glial cell cytokine expression and cellular proliferation.

Interleukin-6 (IL-6) is a B-cell differentiating and T-cell activating cytokine that is expressed in T cells, neutrophils, monocytes, macrophages, and mast cells. Because IL-6 is also synthesized and released by anterior pituitary cells and IL-6 stimulates pituitary hormone release, this cytokine may serve a paracrine or autocrine role within the pituitary. Interleukin-1 beta (IL-1 beta) stimulates IL-6 release from anterior pituitary cells through a mechanism that involves lysophosphatidylcholine (LPC 18:0) generation and protein kinase C activation. In the rat C6 glioma cell line, IL-1 beta synergistically stimulates IL-6 release in the presence of increased intracellular cAMP concentrations. The catecholamines and serotonin also synergistically stimulate IL-6 release in the presence of IL-1 beta. LPC 18:0 synergistically increases IL-6 release in the presence of norepinephrine, and IL-1 beta transiently increases LPC 18:0 formation in C6 cells. Therefore, IL-1 beta induction of LPC 18:0 may lead to increases in IL-6 production via activation of a kinase cascade. The bovine thymic preparation, thymosin fraction 5 (TF5), also stimulates IL-6 release from C6 glioma cells in a protein kinase C-dependent manner. Of interest, TF5 inhibits the proliferation of C6 cells, pituitary adenoma MMQ cells, and promyelocytic HL-60 cells. We suggest that a thymic hormone immune surveillance mechanism may suppress neuroendocrine and hematopoietic tumor formation. Thus, IL-1 beta and certain thymic peptides act to increase IL-6 expression in neuroendocrine cells. The enhanced production of neuroendocrine cytokines may affect hormone secretion, neurotransmission, and the development of certain neurodegenerative disorders (e.g., Alzheimer's disease). The isolation of the active component of TF5 that inhibits neuroendocrine and hematopoietic tumor cell proliferation will provide a potential therapeutic strategy for the treatment of these tumors.