Immunoregulation by Lymphokines: Immune Interferon and Lymphotoxin Induction of Lymphokine Activity in Human Peripheral Blood Leukocyte Cultures

Abstract

Immune responses to tumors are highly complex, with the final outcome dependent upon the interaction of several effector mechanisms within the immune system. Treatment of tumors, as well as other forms forms of immunological disease, has been based on use of nonphysiological agents that nonspecifically alter immunocompetent cell function. The ability of natural products of the immune system to affect immune function has been documented in many studies, in vivo and in vitro (1,2,3). Lymphokines, a group of regulatory substances produced by activated lymphocytes, have potential for development into powerful immunomodulatory tools. Research into mechanisms of lymphokine action has been hampered by lack of sufficient quantities of high purity. The number and properties of chemically distinct lymphokines is unknown. The various induction schemes used to produce lymphokines for study rarely yield a single bioactivity, and there is a strong probability that the interaction of several lymphokines is necessary to successfully modulate an immune function. Supernatants of mitogen-induced human peripheral blood lymphocyte (PBL) cultures contain several lymphokine activities. Analysis of kinetic studies has suggested a correlation in the appearance in culture supernatants of lymphotoxin activity (LT) and immune interferon (Im-IF). The interaction between LT and Im-IF was investigated in a serum-free human PBL culture system.