Rapid IFN-γ expression in lungs of endotoxemic rats is associated with pulmonary tissue damage

The participation of IFN-γ, a lymphocyte-derived cytotone, in endotoxin shock has been well described. On the other hand, little work has been conducted to elucidate at the cellular level, its role in pulmonary tissue damage in an in vivo model of acute endotoxemia. Although there are many reports of increased circulating IFN-γ levels following LPS administration, there are few reports on the critically important tissue expression and/or levels of this cytokine. Indeed, there are virtually no reports of expression or appearance of IFN-γ protein in non-lymphoid tissues in vivo. In our studies, we report that IFN-γ mRNA was detected in rat lungs by Reverse Transcription Polymerase Chain Reaction (RT-PCR) within 3 hours following LPS (salmonella enteritidis, 10 mg/kg, i.v.) administration in anesthetized rats. Intracellular IFN-γ protein was observed by immunostaining techniques in lungs of LPS-treated rats while there was no evidence of IFN-γ in saline treated controls. The expression of IFN-γ was coincident with overt pulmonary tissue damage as observed by histopathological methods. Our results strongly suggest that there is rapid expression of IFN-γ in lungs of rats given LPS and this expression is associated with profound pulmonary tissue damage.