Proinflammatory cytokines and viral respiratory disease in pigs

Abstract

-Swine influenza virus (SIV), porcine respiratory coronavirus (PRCV) and porcine reproductive and respiratory syndrome virus (PRRSV) are enzootic viruses causing pulmonary infections in pigs. The first part of this review concentrates on known clinical and pathogenetic features of these infections. SIV is a primary respiratory pathogen; PRCV and PRRSV, on the contrary, tend to cause subclinical infections if uncomplicated but they appear to be important contributors to multifactorial respiratory diseases. The exact mechanisms whereby these viruses cause symptoms and pathology, however, remain unresolved. Classical studies of pathogenesis have revealed different lung cell tropisms and replication kinetics for each of these viruses and they suggest the involvement of different lung inflammatory responses or mediators. The proinflammatory cytokines interferon-α (IFN-α), tumour necrosis factor-α (TNF-α) and interleukin-1 (IL-1) have been shown to play key roles in several respiratory disease conditions. The biological effects of these cytokines and their involvement in human viral respiratory disease are discussed in the second part of this review. The third part summarises studies that were recently undertaken in the authors' laboratory to investigate the relationship between respiratory disease in pigs and bioactive lung lavage levels of IFN-α, TNF-α and IL-1 during single and combined infections with the above viruses. In single SIV infections, typical signs of swine "flu" were tightly correlated with an excessive and coordinate production of the 3 cytokines examined. PRCV or PRRSV infections, in contrast, were subclinical and did not induce production of all 3 cytokines. Combined infections with these 2 subclinical respiratory viruses failed to potentiate disease or cytokine production. After combined inoculation with PRCV followed by bacterial lipopolysaccharide, both clinical respiratory disease and TNF-α/IL-1 production were markedly more severe than those associated with the respective single inoculations. Taken together, these data are the first to demonstrate that proinflammatory cytokines can be important mediators of viral respiratory diseases in pigs. respiratory coronavirus, PRCV), et le virus du syndrome dysgénésique et respiratoire porcin (porcine reproductive and respiratory syndrome virus, PRRSV) sont des virus enzootiques provoquant des infections pulmonaires chez le porc. Les caractéristiques cliniques et pathogénétiques de ces infections sont données dans la première partie de cette revue. Le SIV est un agent pathogène respiratoire primaire ; les PRCV et PRRSV, en revanche, ne causent que des infections subcliniques en l'absence de complications, mais ils contribuent de manière importante aux maladies respiratoires multifactorielles. Cependant, les mécanismes précis par lesquels ces virus provoquent des symptômes et une pathologie demeurent inconnus. Les études classiques de pathogenèse ont révélé un tropisme pour les cellules pulmonaires et des cinétiques de réplication différents pour...

Lung inflammatory responses

“…Exposure of porcine alveolar macrophages to LPS induces rapid and prolonged production of this chemokine, however, low levels of the proinflammatory cytokine, TNF, are also required [79]. A number of bacteria have been shown to induce CXCL8 production in host species including Mycoplasma hyopneumoniae, M. haemolytica, A. pleuropneumoniae, and swine influenza virus [1,16,126,131,132]. In addition, LPS is a potent inducer of 474 E.L. Thacker CXCL8 [63].…”

Apoptosis in the lungs of pigs infected with porcine reproductive and respiratory syndrome virus and associations with the production of apoptogenic cytokines

“…It has been demonstrated that cytokines, such as tumour necrosis factoralpha (TNF-a) [18], interferon-alpha (IFN-a) [28], interleukin (IL)-1 [6,11] and interleukin-10 [12,33] can induce apoptosis. A PRRSV infection generally fails to induce substantial amounts of IFN-a [1,30,32]. This argues against a possible role of this cytokine in PRRSV-induced apoptosis.…”

“…This argues against a possible role of this cytokine in PRRSV-induced apoptosis. IL-1, however, is produced at high levels in the lungs of PRRSV-infected pigs from 3 till 10 days after inoculation [31] and a weak TNF-a production has been demonstrated at 12 and 13 days after inoculation [32]. Furthermore, the induction of IL-10 mRNA in alveolar macrophages has been reported in PRRSV-infected pigs [29].…”

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

“…By comparison swine influenza (SIV)-specific T cells are detected within 7 dpi (31). Although SIV induces a significant inflammatory response in the respiratory tract that appears related to viral clearance (32), no such inflammation is associated with PRRS (32,33). Despite a delay in virus-specific T cell responses, Ab responses to PRRSV of all major isotypes occur 6 -14 dpi in blood or BAL (34 -36).…”