Macrophage-derived cytokines amplify immune complex-triggered O2-. responses by rat alveolar macrophages.

Abstract

Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are monocyte macrophage-derived hormonelike regulatory proteins that participate in many physiologic and pathophysiologic processes. Several proinflammatory activities have been attributed to these cytokines, but their importance in anatomically compartmentalized inflammatory processes is unclear. The current in vitro studies have been designed to examine modulatory influences of these cytokines on O2-. responses of rat phagocytes implicated as effector cells in immune complex mediated lung injury. Purified human IL-1, recombinant human TNF (rTNF), and culture supernatant from zymosan-activated alveolar macrophages significantly amplified O2-. responses of immune complex-stimulated alveolar macrophages but did not enhance the responses of neutrophils. Equivalent concentrations of IL-1, rTNF, and alveolar macrophage culture supernatant had no direct stimulatory effect on alveolar macrophages as measured by O2-. production. Culture media from unstimulated alveolar macrophages exerted negligible effects on O2-. generation by immune complex-activated alveolar macrophages. These data indicate that O2- responses of immune complex alveolar macrophages can be enhanced by the presence of IL-1, TNF, or media from activated macrophages. It is possible that macrophage products may greatly amplify tissue injury through the enhancement of oxygen radical production.