Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/3/1999
Publication Date: 10/21/2001
Citation: Hediger-Weithaler, B.M., Heussler, V.T., Eicher, R., Zakher, A., Zarlenga, D.S., Canals, A., Gasbarre, L.C., Waldvogel, A.S. 2001. Interferon-gamma and interleukin-4 mrna expression by pbmcs from bvdv seropositive pregnant and non-pregnant cattle. Veterinary Immunology and Immunopathology. 77(3-4):201-212. Interpretive Summary: The production of several cytokines are specifically regulated during normal human and rodent pregnancies. It is postulated that this change or shift in cytokine production is essential to maintain the pregnancy; however, this same regulatory mechanism that maintains the pregnancy also places the mother in an adversarial position with respect to protection against certain diseases. Little is known of the changes in the immune state of pregnant cows and whether they respond as humans and rodents do while pregnant. Since infections with bovine viral diarrhoea virus (BVDV) are common in cattle, administration of this virus to naive and immune pregnant animals offered a system by which the influence of pregnancy on certain types of host immunity could be examined using changes in cytokine transcription profiles as indicators of the immune state of the animal. Results using RNA isolated from peripheral blood suggested that in the presence of a distinct alteration in the immune status of infected animals, bovine, unlike humans and mice, do not show a clear delineation toward a specific type of immune response. This work demonstrated that; 1) the human and rodent model systems cannot be used to predict bovine immune responses to infection; 2) a shift in the immune state of the animal occurred as a result of BVDV infection; and 3) immune system changes in animals resulting from pregnancy provide an important biological target for answers to opportunistic pathogens that manifest themselves in pregnant animals i.e. Neospora caninum.
Technical Abstract: The acceptance of the fetal allograft by pregnant woman and mice seems to be associated with a shift from Th1 dominated to Th2 dominated immune response to certain infectious agents. The goal of this study was to examine cytokine expression in peripheral blood mononuclear cells (PBMCs) from cattle immune to bovine viral diarrhea virus (BVDV) to determine whether pregnancy also has an influence on the type of immune response in this species. Forty-seven heifers and cows between 14 months and 13 years of age were included in this study. Twenty-five were seropositive and 22 seronegative for BVDV. Twelve of the seropositive animals and eleven of the seronegative animals were in the eight month of gestation, the remaining animals were virgin heifers. PBMCs from these animals were analyzed for interferon (IFN)-gamma and interleukin (IL)-4 mRNA expression by competitive RT-PCR after stimulation with a noncytopathic strain of BVDV. Additionally, an ELISA was performed to measure IFN-g in supernatants of stimulated cell cultures. In BVDV seropositive animals, both IFN-g and IL-4 mRNA levels were significantly higher than in BVDV seronegative animals. There was no significant difference in IFN-g and IL-4 mRNA levels between pregnant and non-pregnant animals, nor among the seropositive and seronegative animals. Our results do not allow us to assign a particular type to the immune response against BVDV because expression of both IFN-g and IL-4 was elevated. Furthermore, we could not demonstrate a shift in the cytokine pattern during bovine pregnancy with this approach.