Increased pulmonary secretion of tumor necrosis factor-alpha in calves experimentally infected with bovine respiratory syncytial virus

Abstract

Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease among calves in the Danish cattle industry. An experimental BRSV infection model was used to study the pathogenesis of the disease in calves. Broncho alveolar lung lavage (BAL) was performed on 28 Jersey calves, of which 23 were experimentally infected with BRSV and five were given a mock inoculum. The presence of the cytokine tumor necrosis factor alpha (TNF-alpha) in the BAL fluids was detected and quantified by a capture ELISA. TNF-alpha was detected in 21 of the infected animals. The amount of TNF-alpha in the BAL fluid of calves killed post inoculation day (PID) 2 and 4 was at the same very low level as in the uninfected control animals. Large amounts of TNF-alpha were detected on PID 6, maximum levels of TNF-alpha were reached on PID 7, and smaller amounts of TNF-alpha were seen on PID 8. The high levels of TNF-alpha appeared on the days where severe lung lesions and clinical signs were obvious and the amounts of BRSV-antigen were at their greatest. Although Pasteurellaceae were isolated from some of the BRSV-infected calves, calves treated with antibiotics before and through the whole period of the infection, as well as BRSV-infected calves free of bacteria reached the same level of TNF-alpha as animals from which bacteria were isolated from the lungs. It is concluded that significant quantities of TNF-alpha are produced in the lungs of the calves on PID 6-7 of BRSV infection. The involvement of TNF-alpha in the pathogenesis of, as well as the anti-viral immune response against, BRSV infection is discussed.

Fig. 1

(A–C) Pathology scores and levels of BRSV antigen and TNF-α found in the lungs of calves experimentally infected with BRSV PID 2–8. The figures portray the mean values of calves infected with BRSV (■) where PID 2, 4 and 8 are each based on data from 2 calves, whereas PID 6 and 7 are based on 9 and 8 calves, respectively. Calves, which received the mock inoculum (□) are each represented by one animal PID 2, 4 and 8 and two animals on PID 6 (PID 7 is not done). (A) Pathology scores; based on the estimates of the amount of consolidated tissue present in the lungs of a calf, where the lungs without any lesions are given the score 0, and the lungs with extensive consolidated lung tissue in all lobes are given the score 5 (see Section 2); (B) the presence of BRSV antigen in the lung tissue described by antigen titers (see Section 2); (C) the levels of the cytokine TNF-α detected in BAL by ELISA; ND: not done.