PULMONARY LPS-BINDING PROTEIN (LBP) UP-REGULATION FOLLOWING LPS-MEDIATED INJURY

Background. The acute respiratory distress syndrome (ARDS) causes sign ificant morbidity and mortality among trauma patients. Although multip le factors have been implicated, pulmonary injury in this population m ay be due 60 inflammatory mediators released in response to stimuli su ch as endotoxin (LPS). LBP plays an integral part in LPS-mediated rele ase of inflammatory cytokines and increased local expression of LBP as the result of a primary injury may prime the lung to secondary LPS-me diated damage. Materials and methods. To determine the magnitude of pu lmonary LBP upregulation following LPS injury we challenged rats with either intravenous (IV) or intratracheal (IT) LPS. Animals from each g roup were euthanized at 1, 2, 4, and 8 h postchallenge. Lung LBP and C D14 mRNA levels were assayed by Northern blot. Serum and bronchoalveol ar lavage (BAL) fluid were assayed for inflammatory cytokines (TNF-alp ha, MCP-1, IL-1 beta, IL-6, and IL-10) by ELISA. Results. LBP and CD14 mRNA levels were found to increase significantly in lung tissue after both IV and IT LPS with the TV LPS animals having a greater increase over 8 h. Serum TNF-cw was significantly elevated in the IV LPS group whereas very low levels were detected in the BAL. Only BAL TNF-alpha w as increased in the IT group at 8 h. Conclusion. Local pulmonary LBP a nd CD14 mRNA are both upregulated after either systemic or local LPS e xposure. Such upregulation may render the lung more susceptible to loc al immune overactivation and injury during subsequent exposures to LPS . (C) 1998 Academic Press.