The defence reaction of tissue to injury, infection, or irritation by chemicals or physical agents. Activated macrophages and mast cells in the affected tissue release various signalling molecules (cytokines), including histamine, serotonin, kinins, and prostaglandins. These cause localized dilation of blood vessels so that fluid containing antimicrobial peptides and complement proteins leaks out and blood flow is increased. White blood cells (neutrophils and monocytes) are also attracted to the site. Overall, these responses lead to the classic signs of inflammation: swelling, redness, heat, and often pain. White blood cells, particularly phagocytes, digest pathogens and cell debris, and this process leads to an accumulation of pus, which is gradually consumed by macrophages. Following this immune response (see immunity) a gradual healing process usually follows. More extensive tissue damage may lead to a systemic inflammatory response in which additional white cells are recruited from the bone marrow. Certain cytokines released by activated macrophages can cause fever, in which the body’s thermostat is reset to a higher value. This is thought to speed up chemical reactions and enhance phagocytosis, thereby accelerating the immune response. Septic shock is a life-threatening condition caused by overwhelming systemic inflammation in response to certain bacterial infections.