Biological control of lymphokine function.

Abstract

Lymphokine-dependent reactions are subject to various kinds of biological control. These are most readily studied under conditions in which such reactions are suppressed by systemic administration of a relatively large dose of antigen. This effect is known as desensitization of delayed-type hypersensitivity and mimics the state of clinical anergy seen in various granulomatous and lymphoproliferative diseases. Experiments on this type of immune unresponsiveness have revealed that the suppression is due to several lymphokine-dependent mechanisms. Thus, a large amount of circulating lymphokines generated and released at the initial stage of desensitization may be responsible for the general suppression of hypersensitivity reactions through both the loss of mediator gradients from one tissue to another and the preemption of effector cells. In a subsequent step, monocytes and/or macrophages activated by these lymphokines release arachidonic acid metabolites including prostaglandin (PG) E1 and PGE2, which inhibit both the production and the activities of lymphokines. Lymphokines are also suggested as being capable of directly inducing suppressor cells for lymphokine production, thus exerting a feedback inhibition. These lymphokine-dependent multiple suppression mechanisms are important for regulatory processes in cell-mediated immunity.