BCG PRIMING ENHANCES ENDOTOXIN-INDUCED ACUTE LUNG INJURY INDEPENDENT OF NEUTROPHILS

Bacillus Calmette Guerin (BCC) is known to increase susceptibility to endotoxin in some animal species. We investigated the effect of BCG-pr iming and the role of neutrophils in the priming process on the pathog enesis of acute lung injury caused by intravenously administered Esche richia coli endotoxin (LPS). Guinea pigs were divided into seven group s: (1) control (n = 8), (2) BCG-alone (n = 6), (3) cyclophosphamide (C PA)-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 BCC dose of 8 mg/kg was inj ected subcutaneously 10 d before the study. CPA was administered intra peritoneally to induce peripheral neutropenia. Animals were observed f or 4 h after intravenous administration of 0.2 mg/kg of LPS. The plasm a TNF level was measured 2 h after LPS challenge. Lung wet-to-dry weig ht ratio, [I-125]albumin leakage in lung tissue, differential cell cou nt in bronchoalveolar ravage (BAL) fluid, and histopathologic features were examined immediately after death. Although the LPS-alone group s howed PMN accumulation in lung tissue, neither excess lung water nor i ncreased albumin leakage was induced by this dose of LPS. The BCG+LPS group showed increased lung water, histopathologic edema, and increase s in BAL fluid cell counts and plasma TNF in comparison with the LPS-a lone group. The BCG+CPA+LPS group also showed enhanced lung injury com parable to that seen in the BCG+LPS group. In both the CPA-alone and t he CPA+LPS groups, no parameter was increased as compared with those i n the control group. We conclude that pretreatment with BCC enhances L PS-induced lung injury, possibly through the priming effect of mononuc lear cells but independently of peripheral neutrophils.