Cell mediated immunity and the inflammatory system.

In this review we have considered the evidence for the existence of lymphokines and have focused on the specific mechanisms by which lymphokines modify the behavior of the various inflammatory cells. These mechanisms are based for the most part on in vitro observations. We have therefore discussed in detail data that document an in vivo role for various lymphokines. This evidence is based on experiments falling into two broad categories: the identification of lymphokines in tissue extracts and serum, and the demonstration of various biologic activities of exogenous lymphokines administered locally or systemically. The details of these kinds of experiments have been presented throughout the preceding discussion. The demonstration of lymphokines in vivo adds a new dimension to our ability to study human disease. The detection of migration inhibition factor in serum, for example, is technically simpler than studies of lymphocyte reactivity in patients with altered cellular immunity. Migration inhibition factor has already been found in the serum in several clinical settings, as described. The capacity of exogenous lymphokines for suppressing manifestations of delayed hypersensitivity may provide an explanation for the altered immunoreactivity often observed in some of those diseases. A final comment is in order regarding the significance of lymphokine production in the overall biologic scheme of things. In previous sections we noted that although activation of lymphocytes for lymphokine production by specific antigen is a property of T cells, B cells may be so activated nonspecifically by certain mitogens. Moreover, it has been shown that migration inhibition factor, or substances with similar biologic and physicochemical properties, may be found in certain replicating cultures of nonlymphoid cells. Also, we have recently shown that migration inhibitory activity, as well as certain other lymphokine-like activities such as macrophage and lymphocyte chemotaxis, may appear following the in vitro or in vivo infection of nonlymphoid as well as lymphoid cells by certain viruses. All these results suggest that lymphokine production, rather than "merely" representing an effector mechanism for cell mediated immunity and for certain kinds of helper functions in antibody synthesis, represents a general biologic phenomenon that may play a role in various aspects of host defense. Thus, such mediator substances should be more properly called "cytokines." Lymphokines represent a restricted set of cytokines made by one class of cells (lymphocytes) activated in certain unique ways. In this view the lmyphocyte has acquired some specialized means for triggering such production, not available to other cells.