Alteration of some leukocyte functions following in vivo and in vitro exposure to recombinant bovine alpha- and gamma-interferon.
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-alpha 1 (rBoIFN-alpha 1) and -gamma (rBoIFN-gamma) 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-gamma was less than 20% of that seen with rBoIFN-alpha 1 regardless of whether it was administered intravenously or intramuscularly. Nevertheless, administration of rBoIFN-gamma had a greater effect on leukocyte functions than rBoIFN-alpha 1, both with respect to level and duration of changes. Migration by polymorphonuclear neutrophils (PMN) became suppressed and their generation of O2- was enhanced following rBoIFN treatment. In vitro both rBoIFNs also suppressed migration, whereas the effect on O2- 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.
D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D007371:Interferon-gamma / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D007370:Interferon Type I; D011994:Recombinant Proteins; D013481:Superoxides; D007371:Interferon-gamma