Alpha-Fetoprotein (AFP) and Inflammation: Is AFP an Acute and/or Chronic Phase Reactant?

Abstract

Even though alpha-fetoprotein has long been implicated with inflammation during pregnancy and adult liver dysfunction, the literature lacks a review of such a relationship. Clarification of the role of alpha-fetoprotein in the inflammatory response is explored in the present report regarding AFP's participation as a positive and/or negative phase inflammatory reactant. Inflammation follows a complex succession of vascular changes involving alternations in blood and lymphatic vessels both at local intracellular sites and at the organ (liver) level. The inflammatory response may result in either an acute phase or develop into a chronic phase following injury or insult from foreign bodies, microbes, toxins, carcinogens, or autoimmune self-antigens. The site of inflammation attracts pleiomorphic cell infiltrates which secrete various chemical mediators such as cytokines, chemokines, interferons, histamines, and a host of others. It is herein demonstrated that alpha-fetoprotein can serve both as an acute and a chronic phase reactant depending on its stage of ontogeny. It was found that alpha-fetoprotein functions as a positive acute phase reactant in the embryo, fetus, and placenta during pregnancy. In contrast, alpha-fetoprotein proceeds to function as a negative acute phase protein in the postnatal and adult periods of life, especially following liver dysfunction and toxic insult. In chronic viral-induced inflammation of the liver, especially viral hepatitis, alpha-fetoprotein appears to serve as a positive phase inflammatory reactant.

The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress, Inflammation and Proliferation in Rat Liver, Stomach and Colon: Protective Effect of Ginger Extract

“…AFP exhibits a vital role in the regulation of tumor growth, cell differentiation and proliferation of human hepatoma cells through the AFP receptors (Li et al, 2002). Accordingly, elevated levels of inflammatory cytokines and NOx along with AFP, following DENA administration, support the notion that AFP serves as both an acute and a chronic phase reactant depending on its stage of ontogeny (Mizejewski, 2015). The majority of AFP-producing cancers originate from the stomach, bile duct, and pancreas.…”

Persistent Unresolved Inflammation in theMecp2-308 Female Mutated Mouse Model of Rett Syndrome

“…Apart from their typical APR function, these proteins are also involved in the coagulation process (i.e., KNG1 and A2M) [35, 37], fatty acid and metal binding (i.e., FETA) [39], and innate immune defense and inflammatory modulation (i.e., MBL2) [40]. In particular, KNG1 and A2M are two well-known protease inhibitors.…”

“…KNG1 fragments possess biological activity with moderate to strong correlation with specific diseases (i.e., early progressive renal function decline with type 1 diabetes) [35], while those of murine A2M increase during inflammatory responses and tumor growth [37]. Likewise, FETA shows close connections with the modulation of the proinflammatory response of human keratinocytes [39]. Of note, MBL2 comprises a cysteine-rich domain at the N -terminus followed by a collagen-like domain, a neck region, and a carbohydrate recognition domain at the C -terminus [40].…”