The Effect of Adenosine on the Production of Inflammatory Mediators By Macrophages in Response to Candida Albicans

Mononuclear phagocytic cells (macrophages) are important cells of the immune system that are responsible for host defense to pathogenic organisms and infection. One pathogenic microorganism that can activate macrophages is the dimorphic fungus, Candida albicans. It is a major cause of candidiasis and is responsible for the development of serious, potentially fatal disease in predisposed patients. Upon activation, macrophages secrete inflammatory mediators, including the cytokines tumor necrosis factor alpha (TNF-α) and interleukin 1 (IL-1). Adenosine is an important physiological molecule that can modulate the function of macrophages by altering the amounts of cytokine produced. The effect of adenosine on the production of TNF-α and IL-1 by peritoneal macrophages was studied. Murine peritoneal macrophages stimulated with Candida albicans yeast cells secreted significant amounts of TNF-α and IL-1 over a 14 hr period. Various concentrations of adenosine (10-1000 μM) dose-dependently inhibited the production of TNF-α. Adenosine concentration of 1000 μM increased IL-1 production. The adenosine effect on IL-1 production was proven to be receptor mediated since the non-selective adenosine receptor antagonist (PACPX) was able to block IL-1 production. The results indicate that adenosine differentially affects the production of TNF-α and IL-1 in peritoneal macrophages in response to Candida albicans yeast