Comparison of the systemic and pulmonary inflammatory response to endotoxin of neutropenic and non-neutropenic rats.
BACKGROUND
Neutrophil infiltration commonly occurs in acute lung injury and may be partly responsible for the inflammatory response. However, acute lung injury still occurs in the neutropenic host. The objectives of this study are to determine if inflammation and acute lung injury are worse in neutropenic versus the normal host after endotoxemia.


METHODS
Rats were divided into four groups: 1) control, 2) neutropenic, 3) endotoxemic and 4) endotoxemic and neutropenic. Tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP-2) were measured in the blood, lung lavage and for mRNA in the lung. Arterial blood gases were measured to determine the alveolar-arterial oxygen gradient which reflects on lung injury.


RESULTS
In endotoxemia, the neutropenic rats had lower plasma TNF-alpha (116 +/- 73 vs. 202 +/- 31 pg/ml) and higher plasma MIP-2 (26.8 + 11.9 vs. 15.6 + 6.9 ng/ml) when compared to non-neutropenic rats. The endotoxemic, neutropenic rats had worse lung injury than the endotoxemic, non-neutropenic rats as shown by increase in the alveolar-arterial oxygen gradient (24 +/- 5 vs. 12 +/- 9 torr). However, lavage concentrations of TNF-alpha and MIP-2 were similar in both groups.


CONCLUSIONS
Neutrophils may regulate TNF-alpha and MIP-2 production in endotoxemia. The elevation in plasma MIP-2 in the endotoxemic, neutropenic rat may be secondary to the lack of a neutrophil response to inhibit production or release of MIP-2. In endotoxemia, the severe lung injury observed in neutropenic rats does not depend on TNF-alpha or MIP-2 produced in the lung.
Heidemann
Sabrina M
SM
Department of Pediatric Critical Care Medicine and Clinical Pharmacology, Wayne State University, Detroit, MI, USA. sheidema@med.wayne.edu
Glibetic
Maria
M