Lymphokines, inter leukins, and other immunologica hormones, i.e., the secretory bioregulatory macromolecules of lymphocytes, macrophanges, and other leukocytes are being studied to define their effective anticarcinogenic and tumor cell growth inhibitory activities. Leukoregulin, a newly isolated lymphokine, can prevent carcinogenesis and inhibit tumor cell growth. Anticarcinogenic action is direct, irreversible and occurs without cytotoxicity. Inhibition of tumor cell growth is primarily reversible but can become irreversible due to increased susceptibility of preneoplastic cells to cytolytic destruction by natural killer cells resulting from leukoregulin target cell interaction. Leukoregulin at very high concentrations is also directly cytolytic for tumor cells. The direct acting anticarcinogenic activity of leukoregulin is more potent than the tumor cell inhibitory activity; but by also being able to increase target cell sensitivity to the cytoreductive action of naturally cytoxic lymphocytes, leukoregulin may be an effective homeostatic mechanism for control of carcinogenesis at its later stages of development. Leukoregulin anticarcinogenic, tumor cell growth inhibitory, and cytoreductive sensitizing activities, copurify and are distinct molecularly and biologically from interleukin I, interleukin II, lymphoatoxin, macrophage migration inhibitory factor, macrophage activating factor, and interferon. Leukoregulin alters cell surface conformation, membrane fluidity and permeability, and membrane glycoprotein synthesis with changes in the latter correlating directly in time and quantity to leukoregulin-reduced establishment of the anticarcinogenic state. Leukoregulin induces indentical changes in target cells as are present during natural killer cell cytotoxicity providing strong evidence that it is an intrinsic mediator or element of the natural cytotoxicity reaction and possibly signifying its central role in immunological homeostasis.
