The biology of cachectin/TNF--a primary mediator of the host response.

Inflammation, the most ancient aspect of the host immune response, is surely of great value to the host, insofar as agents that suppress inflam­ mation in a nonspecific fashion predispose to infection. Yet, the inflam­ matory response to invasive organisms may also, if sufficiently intense or inappropriately prolonged, cause injury or death. A delicate balance has thus been achieved, one which clinicians strive to maintain through judicious application of anti-inflammatory medications (e.g. glucocorti­ coids, nonsteroidal anti-inflammatory agents, and cytotoxic drugs). Only recently have we come to understand that many aspects of this primitive response to host invasion are governed by polypeptide hormones, in turn produced by immune effector cells. Moreover, we have come to appreciate the pleiotropic properties of these so-called "cytokines." It would appear that a ' limited number of cytokines are capable of orches­ trating disease states that scarcely resemble one another; among them, endotoxic shock, graft-vs-host disease, cerebral malaria, and cancer cachexia. Cells of monocyte/macrophage lineage play a central role in cytokine ("mono kine") production and so act to modulate many aspects of the inflammatory response. While devoid of specificity and immunologic mem-