Recombinant bovine interferon-gamma as an immunomodulator in dexamethasone-treated and nontreated cattle

Three dosages (0.1, 0.5, and 2.5 mg/animal, subcutaneously), of recombinant bovine interferon-gamma (rBoIFN-gamma) were evaluated for their in vivo influence on neutrophil function and lymphocyte blastogenesis in cattle. The optimal of the three dosages tested (0.5 mg/animal or 1.1 x 10(6) U/animal) was then evaluated for its influence on neutrophils and lymphocytes in both normal and dexamethasone-treated cattle. One animal, which received 2.5 mg of rBoIFN-gamma, died by 24 h after administration due to acute diffuse interstitial pneumonia with interlobular edema and emphysema. The two highest dosages used caused fever at 24 h and the highest dosage caused a decrease in lymphocyte blastogenesis at 24 h after administration. The influence of rBoIFN-gamma on neutrophil function was dose dependent and depended on the baseline values for neutrophil function. Random migration by neutrophils was consistently inhibited in animals that received 0.5 mg or more of rBoIFN-gamma. Staphylococcus aureus ingestion and antibody-dependent cell-mediated cytotoxicity by neutrophils was enhanced by rBoIFN-gamma treatment in both dexamethasone-treated cattle and in nondexamethasone-treated cattle, which had relatively low values for these parameters before treatment. Iodination by neutrophils was also enhanced by rBoIFN-gamma when either a suboptimal concentration of neutrophil stimulant was used or when the cattle were treated with dexamethasone. In summary, the rBoIFN-gamma had greater immunomodulator activity in immunosuppressed than in normal cattle. The in vivo influence of rBoIFN-gamma therefore depends on the physiologic status of the animal.