ANIMAL-MODELS FOR THE BIOLOGICAL EFFECTS OF CONTINUOUS HIGH CYTOKINE LEVELS

Transgenic animals or animals engrafted with retrovirus-derived expression vectors provide models for studying the in vivo effects of high and continuous serum levels of cytokines. Studies employing these models in order to analyze the biological effects for granulocytes-macrophages colony-stimulating factors (CSFs), granulocytes of interleukin (IL-)2, IL-3, IL-6 and erythropoietin are reviewed. In all of these models, overexpression of the different cytokines achieved by use of these approaches resulted in syndromes that were related to nonneoplastic hyperplasia of the respective target cell population. In some but not all models, these syndromes were lethal, mostly due to hypercellularity. These models allow conclusions about the biological effects of very high and continuous levels of these substances as well as about their regulation in different tissues.