Pulmonary expression of tumor necrosis factor alpha, interleukin-1 beta, and interleukin-8 in the acute phase of bovine pneumonic pasteurellosis

Vet Pathol. 2001 May;38(3):297-310. doi: 10.1354/vp.38-3-297.


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 (TNFalpha), interleukin-1 beta (IL-1beta), 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 TNFalpha, IL-1beta, 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 occured 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 TNFalpha was least expressed. Expression of TNFalpha was restricted to alveolar macrophages. Alveolar and interstitial macrophages produced IL-1beta 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-1beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern / veterinary
  • Bronchoalveolar Lavage Fluid / cytology
  • Cattle
  • Cattle Diseases / metabolism*
  • Cattle Diseases / microbiology
  • Cattle Diseases / pathology
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay / veterinary
  • Image Processing, Computer-Assisted
  • In Situ Hybridization / veterinary
  • Interleukin-1 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Lung / metabolism*
  • Lung / microbiology
  • Lung / pathology
  • Male
  • Mannheimia haemolytica / chemistry
  • Mannheimia haemolytica / genetics
  • Mannheimia haemolytica / growth & development*
  • Pasteurellosis, Pneumonic / metabolism*
  • Pasteurellosis, Pneumonic / microbiology
  • Pasteurellosis, Pneumonic / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Cytokines
  • Interleukin-1
  • Interleukin-8
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha