Inflammatory Cytokines, Pleuropneumonia Infection and the Effect of Dexamethasone

Abstract

Objectives:Actinobacillus pleuropneumoniae causes an often fatal infection of swine due to pleuropneumonia. To determine if inflammatory cytokines are associated with A. pleuropneumoniae-induced pneumonia, infected and noninfected animals were concomitantly administered saline or dexamethasone. Methods: Twenty-four swine were treated with saline, A. pleuropneumoniae, dexamethasone, or A. pleuropneumoniae and dexamethasone (n = 6). The plasma levels of TNF-α, IL-1β, IL-6, IL-8, and IL-10 were examined through time of necropsy (72 h). Gross pathology and histopathology was performed on all animals. Results: Dexamethasone had no effect on A. pleuropneumoniae-induced increases in lung/body weight ratios. Gross pathology of the infected pigs included fibrinous pleuropneumonia with necrosis and hemorrhage in a focal to a multifocal pattern. Histopathology of infected pig lungs revealed necrotizing extensive, fibrinopurulent pneumonia with edema and fibrinopurulent pleuritis. Plasma IL-6 levels were elevated in A. pleuropneumoniae-infected animals beginning 6 h after infection. Dexamethasone treatment did not alter A. pleuropneumoniae-induced plasma IL-6 levels. A. pleuropneumoniae infection did not elicit plasma levels of TNF-α, IL-1β, IL-8, or IL-10. Conclusion: These results suggest that the pneumonia caused by A. pleuropneumoniae infection is not due to the release of systemic inflammatory cytokines.

Multiplex analysis of pro-inflammatory cytokines in serum of Actinobacillus pleuropneumoniae-infected pigs

“…of A. pleuropneumoniae. These results are inconsistent with some previous reports, in which no systemic changes in TNF-α and IL-1β could be detected in A. pleuropneumoniaeinfected pigs (Fossum et al, 1998;Balaji et al, 2002;Myers et al, 2004). Yet, Huang et al (1999) described an increase in TNF-α as well as IL-1β after both an in vitro and in vivo stimulation and infection with A. pleuropneumoniae, respectively.…”

“…In the current study, 80% of the pigs showed a marked IL-6 response following experimental infection with A. pleuropneumoniae and a maximal mean IL-6 concentration was recorded 10 h p.i. These findings are largely in agreement with other reports (Fossum et al, 1998;Lauritzen et al, 2003;Myers et al, 2004), including a very recent one from Tambuyzer et al (2014).…”

“…The sequence of cytokine release following LPS administration is quite straightforward (Gerros et al, 1993). In contrast, the substantial biological variations observed between outbred animals in a bacterial infection model, which was also obvious in our experiments remain of major concern (Fossum et al, 1998;Huang et al, 1999;Myers et al, 2004). Moreover, the mode of infection, bacterial dosage, strain and associated virulence factors might also contribute to a different outcome (Huang et al, 1999;Balaji et al, 2002).…”

“…The first 18 h p.i. were selected for analysis using the CBA 3-plex cytokine assay, as the induction of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 can be expected immediately after infection (Baarsch et al, 1995;Fossum et al, 1998;Huang et al, 1999;Myers et al, 2004). Indeed, TNF-α reached a maximal concentration at 12 h p.i., while IL-1β levels increased steadily p.i.…”

“…A. pleuropneumoniae has a multifactorial pathogenicity, involving different secreted and non-secreted virulence factors, including lipopolysaccharide (LPS), cytotoxins (Apx toxins), hemolysin, proteases, host and environmental factors (Haesebrouck et al, 1997;Huang et al, 1998;Chiers et al, 2010). Reports on systemic cytokine production following experimental infections with A. pleuropneumoniae in pigs are not as straightforward (Fossum et al, 1998;Huang et al, 1999;Balaji et al, 2002;Myers et al, 2004). Only IL-6 has been consistently detected in the majority of infected pigs and has consequently been put forward as a valuable marker for bacterial infections (Fossum et al, 1998).…”