Alteration of Some Leukocyte Functions Following In Vivo and In Vitro Exposure to Recombinant Bovine Alpha-and Gamma-Interferon

Abstract

Bovine interferons (BoIFNs) produced by recombinant DNA technology are currently being evaluated for their prophylactic effect against virus-induced respiratory disease in cattle. In this context experiments were conducted to compare blood levels of recombinant bovine interferon-alpha₁ (rBoIFN-α₁) and -gamma (rBoIFN-γ) following intravenous and intramuscular injection to healthy calves, and to assess the effect on the immune response. Maximum serum level of IFN obtained with rBoIFN-γ was less than 20% of that seen with rBoIFN-α₁ regardless of whether it was administered intravenously or intramuscularly. Nevertheless, administration of rBoIFN-γ had a greater effect on leukocyte functions than rBolFN-α₁, both with respect to level and duration of changes. Migration by polymorphonuclear neutrophils (PMN) became suppressed and their generation of O⁻ ₂ was enhanced following rBolFN treatment. In vitro both rBoIFNs also suppressed migration, whereas the effect on O⁻ ₂ generation was minimal with suppression seen only at very high doses. Lymphocyte proliferation was also suppressed 24 h after IFN injection, and this effect could be reversed by exogenous interleukin-2 (IL-2) added to the cultures. In experiments designed to elucidate the mechanism of lymphocyte-suppression, it was found that in vitro treatment with rBoIFNs can induce suppressor cells, which may act by competing for IL-2. The combination of in vivo and in vitro experimental models used here could prove useful in additional studies to further delineate the mechanisms involved in the immunomodulatory effects of IFNs.