Excessive Immune Function in Animals
There are many ways by which excessive immune function can cause disease or death. These include excessive innate responses, excessive adaptive responses, autoimmune diseases, and tumors of the immune system.
Although acute inflammation is a defensive process and central to innate immunity, it may occur without appropriate provocation and in locations where it causes discomfort, tissue damage, or systemic disease. This results in significant morbidity and resulting disability.
In severe infections or after massive tissue damage, large amounts of cytokines and reactive oxygen and radicals enter the bloodstream and cause a form of shock known as systemic inflammatory response syndrome.
Septic shock is the name given to the systemic inflammatory response syndrome caused by severe infections and associated with trauma, ischemia, and tissue injury. Animals with severe infections may generate large quantities of cytokines, most notably IL-1, TNF-alpha, IL-8, and IL-6. This massive cytokine release has been called “a cytokine storm.” High doses of cytokines are toxic and induce acidosis, fever, lactate release in tissues, an uncontrollable drop in blood pressure, elevation of plasma catecholamines, and eventually renal, liver, and lung injury and death. The procoagulant–anticoagulant balance is upset, so endothelial procoagulant activity is enhanced, while many anticoagulant pathways are inhibited, leading to DIC and capillary thrombosis.
All these effects are initiated by excessive triggering of toll-like receptors (TLRs), leading to a massive and uncontrolled release of cytokines. The cytokines damage vascular endothelial cells, activating them so that procoagulant activity is enhanced, which results in blood clotting. The nitric oxide causes vasodilation and a drop in blood pressure. The widespread damage to vascular endothelium eventually causes organ failure. Multiple organ dysfunction syndrome is the end stage of severe septic shock. It is characterized by hypotension, insufficient tissue perfusion, uncontrollable bleeding, and organ failure caused by hypoxia, tissue acidosis, tissue necrosis, and severe local metabolic disturbances. The severe bleeding is due to DIC. The sensitivity of mammals to septic shock varies greatly. Species with pulmonary intravascular macrophages such as the cat, horse, sheep, and pig tend to be more susceptible than dogs.