BCG priming enhances endotoxin-induced acute lung injury independent of neutrophils

Sadatomo Tasaka, Akitoshi Ishizaka, Tetsuya Urano, Koichi Sayama, Fumio Sakamaki, Hidetoshi Nakamura, Takeshi Terashima, Yasuhiro Waki, Kenzo Soejima, Yoshitaka Oyamada, Seitaro Fujishima, Minoru Kanazawa

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Bacillus Calmette Guerin (BCG) is known to increase susceptibility to endotoxin in some animal species. We investigated the effect of BCG-priming and the role of neutrophils in the priming process on the pathogenesis of acute lung injury caused by intravenously administered Escherichia call endotoxin (LPS). Guinea pigs were divided into seven groups: (1) control (n = 8), (2) BCG-alone (n = 6), (3) cyclophosphamide (CPA)-alone (n = 6), (4) CPA+LPS (n = 6), (5) LPS-alone (n = 6), (6) BCG+LPS (n = 6), and (7) BCG+CPA+LPS (n = 6). A BCG dose of 8 mg/kg was injected subcutaneously 10 d before the study. CPA was administered intraperitoneally to induce peripheral neutropenia. Animals were observed for 4 h after intravenous administration of 0.2 mg/kg of LPS. The plasma TNF level was measured 2 h after LPS challenge. Lung wet-to-dry weight ratio, [125I]albumin leakage in lung tissue, differential cell count in bronchoalveolar lavage (BAL) fluid, and histopathologic features were examined immediately after death. Although the LPS-alone group showed PMN accumulation in lung tissue, neither excess lung water nor increased albumin leakage was induced by this dose of LPS. The BCG+LPS group showed increased lung water, histopathologic edema, and increases in BAL fluid cell counts and plasma TNF in comparison with the LPS- alone group. The BCG+CPA+LPS group also showed enhanced lung injury comparable to that seen in the BCG+LPS group. In both the CPA-alone and the CPA+LPS groups, no parameter was increased as compared with those in the control group. We conclude that pretreatment with BCG enhances LPS-induced lung injury, possibly through the priming effect of mononuclear cells but independently of peripheral neutrophils.

Original languageEnglish
Pages (from-to)1041-1049
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Issue number3
Publication statusPublished - 1995 Sept

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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