We have isolated from calf serum a protein with an apparent M r of 120,000. The protein was detected by using antibodies against major acute-phase protein in pigs with acute inflammation. The amino acid sequence of an internal fragment revealed that this protein is the bovine counterpart of ITIH4, the heavy chain 4 of the inter-alpha-trypsin inhibitor family. The response of this protein in the sera was determined for animals during experimental bacterial and viral infections. In the bacterial model, animals were inoculated with a mixture of Actinomyces pyogenes, Fusobacterium necrophorum, and Peptostreptococcus indolicus to induce an acute-phase reaction. All animals developed moderate to severe clinical mastitis and exhibited remarkable increases in ITIH4 concentration in serum (from 3 to 12 times the initial values, peaking at 48 to 72 h after infection) that correlated with the severity of the disease. Animals with experimental infections with bovine respiratory syncytial virus (BRSV) also showed increases in ITIH4 concentration (from two-to fivefold), which peaked at around 7 to 8 days after inoculation. Generally, no response was seen after a second infection of the same animals with the virus. Because of the significant induction of the protein in the animals in the mastitis and BRSV infection models, we can conclude that ITIH4 is a new positive acute-phase protein in cattle.The acute-phase response occurs in animals as a consequence of infection, inflammation, or trauma. It is a nonspecific response mediated by inflammation-related cytokines (mainly by interleukin-6 [IL-6], IL-1, and tumor necrosis factor alpha) and is characterized by several systemic reactions, including fever, catabolism of muscle protein, alterations in sleep and appetite patterns, and changes in the concentrations of a group of serum proteins called acute-phase proteins (APP) (3,22,27,40).APP have been studied extensively in humans and in many animal species, mostly rats (38), though the panel of these proteins is probably not complete. The APP response differs among species. For domestic animals, the studies on APP are relatively recent (reviewed in reference 18). For cattle, several APP, including serum amyloid A, haptoglobin, alpha-1-acid glycoprotein, and alpha-1-proteinase inhibitor (alpha-1-antitrypsin), have been shown to increase in different inflammatory processes, in both in vivo (9,14,18,20,23,25,32) and in vitro models (2, 31). The course of infection in human patients is monitored by the determination of APP in blood samples (43), and a similar clinical use has been proposed for veterinary medicine (15,18,26) as well as for monitoring the health status of animals during farm production and at slaughter (42).In previous works from our laboratory, a new 120-kDa plasma glycoprotein, designated major acute-phase protein or pig MAP, was described as an APP occurring in pigs with turpentine-induced inflammation (16,29). This protein, which is also called porcine inter-alpha-trypsin inhibitor human-related protein (pig IHRP) (...