The activation of macrophages and newly recruited monocytes appears to be common to both Crohn's disease and ulcerative colitis, despite different inductive stimuli. Similar activation occurs acutely during the course of invasive intestinal infections such as shigellosis, but is then usually downregulated. The macrophage cytokines tumor necrosis factor-alpha and interleukin-1 (IL-1) are centrally involved in the local inflammatory response, and blockade of either cytokine greatly attenuates the inflammatory lesion. Induction of focal vascular thrombosis and matrix degradation are thought to be an important component of this focal damage. Both cytokines and IL-6 are now recognized to contribute to the systemic effects of intestinal disease, including growth suppression, anorexia, and chronic anemia. Disturbance of sleep patterns, mood, and affect may also occur, and recent evidence points towards bidirectional interplay between macrophage cytokines and central nervous system function.