New insights into the biology of the acute phase response

Innate or natural immunity is a highly conserved defense mechanism against infection found in all multicellular organisms. The acute phase response is the set of immediate inflammatory responses initiated by pattern recogniti on molecules. These germ cell-encoded proteins recognize microbial pathogen s based on shared molecular structures and induce host responses that local ize the spread of infection and enhance systemic resistance to infection. I nnate immunity also influences the initiation and type of adaptive immune r esponse by regulating T cell costimulatory activity and antigen presentatio n by antigen presenting cells and by influencing mediator production, which affects lymphocyte function and trafficking. Acute phase protein concentra tions rapidly increase after infection, and their production is controlled primarily by IL-6- and IL-l-type cytokines. The acute phase proteins provid e enhanced protection against microorganisms and modify inflammatory respon ses by effects on cell trafficking and mediator release. For example, serum amyloid A has potent leukocyte activating functions including induction of chemotaxis, enhancement of leukocyte adhesion to endothelial cells, and in creased phagocytosis. The constellation of inflammatory responses seen afte r endotoxin administration to humans represents an in vivo model of the acu te phase response. Studies with inflammatory modifying agents, such as solu ble dimeric TNF receptor and IL-10, show that these responses are not depen dent on a single mediator but result from multiple overlapping inflammatory pathways. Understanding the factors that initiate and alter the magnitude and duration of the acute phase response represents an important step in th e development of new therapies for infectious and inflammatory diseases.