title: Interleukin-12 (IL-12) ameliorates the effects of porcine respiratory and reproductive syndrome virus (PRRSV) infection.
abstract: Porcine respiratory and reproductive syndrome virus (PRRSV) disease, one of the most economically significant viral diseases in the swine industry, is characterized by miscarriages, premature farrowing, stillborn pigs, and respiratory disease associated with death and chronic poor performance of nursing and weaned pigs. Interleukin-12 (IL-12) is a key component in driving the development of cell-mediated immunity as well as stimulating interferon-gamma (IFN-gamma) production from T cells and natural killer cells. Although some studies have investigated the use of IL-12 as a vaccine adjuvant in swine, little is known about its effectiveness as a treatment against viral diseases in swine. The present study investigated whether recombinant porcine IL-12 (rpIL-12) enhances the immune response and thereby diminishes the effects of PRRSV infection in young pigs. Interestingly, in vitro experiments demonstrated that rpIL-12 is capable of inducing swine pulmonary alveolar macrophages (PAMs), the target cells of PRRSV, to produce IFN-gamma in a dose and time dependent manner. In addition, in vitro studies also revealed that rpIL-12 treatment was capable of significantly reducing PRRSV viral titers in PAMs. In vivo administration of rpIL-12 significantly decreased PRRSV titers in the lungs and blood of infected animals. Furthermore, treatment with rpIL-12 prevented significant growth retardation in PRRSV-infected animals. Finally, in response to viral antigen recall challenge, PAMs isolated from rpIL-12-treated/PRRSV-infected animals produced greater amounts of IFN-gamma and lesser amounts of interleukin-10 than PAMs isolated from non-rpIL-12-treated/PRRSV-infected animals. Taken together our data indicate that treatment with rpIL-12 may provide an effective approach to control or ameliorate PRRSV-induced disease in swine.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN, USA.
authors.forename: Quincy L
authors.initials: QL
authors.lastname: Carter
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Curiel
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D016679:Genome, Viral; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008297:Male; D019318:Porcine Reproductive and Respiratory Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D011247:Pregnancy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D034421:Sus scrofa
chemical_list: D000956:Antigens, Viral; D007155:Immunologic Factors; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma