Haptoglobin (Hp) is commonly believed to have as its main function the capacity to scavenge hemoglobin, thus protecting the body from oxidation, iron loss, and kidney damage during acute hemolysis. In laboratory medicine, serum Hp levels are used as a marker for evaluation of hemolysis. However, Hp is also an acute phase protein (APP) whose synthesis is induced in the liver by IL-6 and corticosteroids as a result of inflammation.

We here discuss that Hp also affects the functions of different leukocyte types. A more clear picture of the degree to which it takes part in the orchestration of immune reactions is now emerging. Hp predominantly seems to dampen the proinflammatory functions of macrophages. It decreases cytokine release by macrophages and T cells. In animal models, Hp deficiency improves resistance against microbial invasion, but also enhances susceptibility to tissue danage in autoimmune and allergic diseases. An understanding of its mechanisms of action in inflammatory disease states may bring new insight into the role of APP in general, and may open opportunities for future therapeutic strategies.