In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding

Abstract

The early cytokines interferon-alpha (IFN-alpha), tumour necrosis factor-alpha (TNF-alpha), interleukin-1, -6 and -8 (IL-1, -6, -8) are produced during the most early stage of an infection. The activities of these cytokines have been studied extensively in vitro and in rodents, but in vivo studies on the role of these cytokines in infectious diseases of food animals are few. This review concentrates on in vivo studies of cytokine involvement in infectious respiratory diseases of swine, with an emphasis on viral infections. First evidence for the role of early cytokines in pneumonia in swine came from experimental infections with Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. The role of TNF-alpha and IL-1 in the symptoms and pathology of porcine pleuropneumonia has recently been proven by use of an adenovirus vector expressing the anti-inflammatory IL-10. In the authors' laboratory, studies were undertaken to investigate the relationship between viral respiratory disease and bioactive lung lavage levels of IFN-alpha, TNF-alpha, IL-1 and IL-6. Out of three respiratory viruses-porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV)-only SIV induced acute respiratory disease and severe lung damage by itself. Disease and lung pathology were tightly associated with the simultaneous production of IFN-alpha, TNF-alpha, IL-1 and IL-6. In challenge studies of SIV-vaccinated pigs, levels of IFN-alpha, TNF-alpha and IL-6, but not IL-1 were correlated with clinical and virological protection. Multifactorial respiratory disease was reproduced by combined inoculations with PRCV or PRRSV followed by LPS from Escherichia coli. In comparison with the respective single inoculations, which were subclinical, there was a true potentiation of disease and production of TNF-alpha, IL-1 and IL-6. TNF-alpha and IL-6 were best correlated with disease. In further studies, we will use more specific strategies to dissect the role of cytokines during viral infections.

Fig. 1

Kinetics of respiratory signs, lung virus titres, neutrophils and cytokines in BAL fluids after intratracheal inoculation of gnotobiotic pigs with the Sw/Belgium/1/83 (H1N1) SIV.

Fig. 2

Comparative profiles of respiratory signs, lung virus titres, neutrophils and cytokines in BAL fluids after inoculation with PRCV followed 24 h later by LPS, or with PRCV or LPS only.