NEUTROPHIL MACROPHAGE INTERACTION - A PARADIGM FOR CHRONIC INFLAMMATION

Autoimmune diseases, such as rheumatoid arthritis and inflammatory bow el disease are characterized by chronic inflammatory responses resulti ng in tissue damage. These diseases have a number of common denominato rs including: abnormal cytokine expression, aberrant antigen-antibody complexes, T cell anomalies, and increased numbers of neutrophils and macrophages. We propose that the interaction between neutrophils and m acrophages induces a state of chronic inflammation which contributes t o the disease state. One of the central players in this scenario is my eloperoxidase (MyPo). This enzyme functions in the 'cytotoxic triad' a nd is involved in cell killing. Studies done by the present investigat ors have shown that MyPo, which is released from neutrophils, induces macrophages to secrete interleukin-1, interferon alpha beta and tumor necrosis factor alpha. Furthermore, our studies have suggested a major immunoregulatory role of this enzyme. We propose that the release of MyPo from neutrophils and subsequent binding to macrophages initiates a cascade of events which enhance the production of reactive oxygen in termediates and cytokine expression resulting in the chronic inflammat ory state associated with autoimmune diseases.