Pulmonary Expression of Tumor Necrosis Factor Alpha, Interleukin-1 Beta, and Interleukin-8 in the Acute Phase of Bovine Pneumonic Pasteurellosis

Abstract

Abstract. Inflammatory cytokines are suspected to contribute to the pathogenesis of bovine pneumonic pasteurellosis (BPP) through neutrophil recruitment, leukocyte activation, and the induction of a broad array of soluble inflammatory mediators. An in vivo experimental model of BPP was used to characterize the pulmonary expression kinetics of tumor necrosis factor alpha (TNF␣), interleukin-1 beta (IL-1␤), and interleukin-8 (IL-8) genes and proteins during the acute phase of disease development. Cytokine expression in bronchoalveolar lavage (BAL) fluid, BAL cells, and pneumonic lung parenchyma was quantitated by northern blot analysis, enzyme-linked immunosorbent assay (ELISA), and in situ hybridization at 2, 4, 8, 16, and 24 hours after endobronchial inoculation of Pasteurella (Mannheimia) haemolytica. Expression of TNF␣, IL-1␤, and IL-8 was significantly increased in the airways and lung lesions of infected calves as compared with mock-infected controls. Although kinetic patterns varied, peak levels of cytokine mRNA occurred within 8 hours postinfection (PI), and peak cytokine concentrations occurred within 16 hours PI. In all samples, IL-8 was expressed to the greatest extent and TNF␣ was least expressed. Expression of TNF␣ was restricted to alveolar macrophages. Alveolar and interstitial macrophages produced IL-1␤ and IL-8 in the first 4 hours; bronchial and bronchiolar epithelial cells were also significant sources of IL-8 during this period. By 8 hours PI, neutrophils were the dominant source of both IL-1␤ and IL-8. These findings demonstrate a spatial and temporal association between pulmonary expression of inflammatory cytokines and acute lung pathology, supporting the hypothesis that cytokines contribute to inflammatory lung injury in BPP.

Mannheimia haemolytica

“…4). 69,83,90,126 To overcome host defenses, M haemolytica has evolved a powerful mechanism of LKT-mediated cytotoxicity of the leukocytes involved in the innate and adaptive immune responses. 18 LKT forms transmembrane pores in bovine lymphocytes, neutrophils, macrophages, mast cells, and platelets, eventually causing oncotic cell cytotoxicity (Fig.…”

The Functional State of Neutrophils Correlates With the Severity of Renal Dysfunction in Children With Hemolytic Uremic Syndrome

“…The lower levels in spontaneous apoptosis found in severe cases of HUS could contribute, at least in part, to the neutrophilia usually observed in these patients. PMN are a very important source of cytokines in vivo, including IL-8, a cytokine that activates PMN and inhibits their apoptosis (17,25,26). However, IL-8 seems not to be involved in preventing apoptosis of HUS PMN, since there was no correlation between the plasmatic level of IL-8 and the percentage of apoptosis.…”

The Bovine Lung in Biomedical Research: Visually Guided Bronchoscopy, Intrabronchial Inoculation and <em>In Vivo</em> Sampling Techniques

“…In calves, experimental bronchoscopy was described in 1968 for the first time 37 . The intrabronchial application of pathogens was suggested by Potgieter et al as a reliable method to produce lower respiratory tract disease in calves 38 and is now a widespread method in bovine research 34,39,40 . Intrabronchial inoculation of a defined amount of the pathogen under videoendoscopic control allows for selective placement of the infectious agent in the lung.…”

“…Endoscopic inoculation of various pathogens has been described, such as C. psittaci [32][33][34] , Pasteurella haemolytica [38][39][40]42 , Haemophilus somni 55 , and bovine viral diarrhea virus 44 . Also, the sites of pathogen deposit in the lung can be adapted to the desired model.…”