There are three different ways by which excessive immune function can cause disease or death. These include excessive inflammatory responses, allergic diseases, and autoimmune diseases.
Although acute inflammation is a defensive process and central to innate immunity, it may occur without apparent provocation and in locations where it causes serious discomfort, tissue damage, or systemic disease. This may result in substantial morbidity and disability.
Systemic Inflammatory Response Syndrome in Animals
In severe infections or after massive tissue damage, excessive amounts of cytokines and reactive oxygen radicals enter the bloodstream and cause a form of shock known as systemic inflammatory response syndrome (SIRS).
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, tumor necrosis factor (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.
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 thrombosis along with concurrent vasodilation and a drop in blood pressure. The widespread damage to vascular endothelium eventually causes organ failure. 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.
