Summary auto-generated
This article investigates the role of two cytokines, TNF-α (tumor necrosis factor-alpha) and IL-1β (interleukin-1 beta), in the inflammatory response to lipopolysaccharide (LPS) in porcine respiratory tract. The researchers used pigs infected with porcine respiratory coronavirus (PRCV) and examined the kinetics of TNF-α and IL-1β production in bronchoalveolar lavage (BAL) fluid following LPS challenge at various time points post-infection. Both cytokines were induced by LPS, with TNF-α appearing earlier and at higher concentrations than IL-1β. The study demonstrated that PRCV infection primed the respiratory tract, enhancing subsequent TNF-α and IL-1β responses to LPS. Using blocking antibodies and in vitro experiments with isolated alveolar macrophages, the authors showed that TNF-α and IL-1β production was mediated by different cellular sources and regulatory mechanisms. The findings suggest that prior viral infection sensitizes the innate immune system to bacterial endotoxin, potentially explaining increased severity of secondary bacterial infections following respiratory virus exposure in pigs.
Key findings
- TNF-α and IL-1β were both induced by LPS challenge, with TNF-α appearing earlier and at higher concentrations than IL-1β in bronchoalveolar lavage fluid
- Prior PRCV infection significantly enhanced and prolonged the TNF-α and IL-1β responses to subsequent LPS exposure, demonstrating priming of the respiratory immune system
- TNF-α and IL-1β production involved different cellular sources and regulatory mechanisms, suggesting distinct inflammatory pathways activated by the viral-bacterial co-challenge model
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Abstract
This study examined whether exposure of pigs to both porcine respiratory coronavirus (PRCV) and bacterial lipopolysaccharide (LPS) can potentiate respiratory disease and lung secretion of tumour necrosis factor-α (TNF-α) and interleukin-1 (IL-1). Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with PRCV, with LPS from Escherichia coli O111:B4 (20 µg/kg), or with a combination of the two, and killed at set times after inoculation. Clinical signs, virus replication and (histo)pathological changes in the lungs, percentage of neutrophils and bioactive TNF-α and IL-1 in broncho-alveolar lavage (BAL) fluids were examined. The effects of separate virus or LPS inoculations were subclinical and failed to induce high and sustained cytokine levels. In a preliminary study, pigs were inoculated with PRCV and then with LPS 24 h later and killed sequentially. Severe respiratory disease and significantly enhanced TNF-α titres (2083601 U/ml versus 4089 U/ml after LPS only) were seen during the first 12 h after LPS inoculation. IL-1 levels (1061631 U/ml versus 28654 U/ml after LPS only) were also increased, but persisted for longer after clinical recovery than TNF-α. In a second study, pigs were inoculated with PRCV and subsequently with LPS at various time intervals ranging from 0 to 24 h, and killed 5 h after inoculation with LPS. A time interval of at least 12 h between inoculations was necessary for prominent respiratory signs to develop. Production of TNF-α, but not IL-1, was also dependent on the time interval between inoculations and was tightly correlated with disease. Lung neutrophil infiltration and pathological changes were comparable after combined PRCV-LPS and single LPS inoculations, and were not associated with disease. These data show that exposure to high endotoxin concentrations in swine buildings can precipitate respiratory disease in PRCV-infected pigs, and that TNF-α is probably an important mediator of these effects. This is the first in-vivo demonstration of synergy between respiratory viruses and LPS.