ISSN:
1059-910X
Keywords:
Escherichia coli
;
Candida albicans
;
Staphylococcus aureus
;
Bacteremia
;
Candidemia
;
Cytokines
;
TNF
;
Adult respiratory distress syndrome
;
Pulmonary edema
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Natural Sciences in General
Notes:
We compared physiological and ultrastructural indices of acute lung injury (ALI) during septic shock caused by taxonomically diverse pathogens to distinguish ALI due to endogenous inflammatory mediators vs. microbial exotoxins or other factors. Conscious rats were infected i.v. with gram-negativeEscherichia coli(EC, serotype 055:B5), exotoxin-C producing gram-positiveStaphylococcus aureus (SA), or yeast-phaseCandida albicans(CA, a clinical isolate). Viable inocula of 1010 EC, 1010 SA, or 109 CA caused lethal shock in 〈24 h, but distinct types of ALI were noted after bacteria vs. fungi. Within 0.5 h of EC infection, leukocytes marginated in the lung vasculature; by death at 6-14 h, animals were hyperoxemic but not acidemic, and showed slight interstitial edema with increased wet/dry weight ratios (W/D = 5.22 ± 0.10, mean ± SE, vs. 4.86 ± 0.07 in controls, P 〈0.05). Similarly mild ALI occurred after 1010 SA. In contrast, within 0.5 h of CA infection, yeast were visible within lung intravascular leukocytes. By death at 6-12 h, CA animals showed hyperoxic acidemia and moderate ALI with capillary obstruction, interstitial hemorrhage, and elevated lung W/D (5.52 ± 0.13, P 〈0.05 vs. controls) associated with yeast-mycelial transformation. Prior neutropenia accelerated mortality and worsened ALI after CA, with hypoxemic acidemia, increased lung W/D (7.23 ± 0.34, P 〈0.05 vs. other groups), capillary occlusion, perivascular and alveolar hemorrhage, and septal disruption by mycelia. Bacteremia induced large increases in serum tumor necrosis factor-α (TNF) and interleukin-1α within 1.5 h, but these cytokines remained low in CA animals, even at death. Neither survival nor ALI after EC or CA was altered by pentoxifylline, which attentuated TNF production, or by cyclooxygenase inhibition with ibuprofen. Thus, overall ALI severity correlated with physiological indices of pulmonary function, but ultrastructural changes correlated better with pathogen type than circulating cytokine or eicosanoid mediators. Whereas lethal bacteremia induced early cytokinemia and mild ALI with or without bacterial exotoxins, moderate ALI apparently was mediated by fungal exotoxins during lethal candidemia, which worsened during neutropenia due to enhanced mycelial proliferation.© 1993 Wiley-Liss, Inc.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jemt.1070260512
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