Effect of CD14 blockade in rabbits with Escherichia coli pneumonia and sepsis

CD14, a pattern recognition receptor found on myeloid cells, is a critical component of the innate immune system that mediates local and systemic host responses to Gram-negative and Gram-positive bacterial products. Previous studies in normal animals have tested the effect of CD14 blockade on the sy stemic response to i.v. LPS. The goals of the study were to determine wheth er CD14 blockade protected against the deleterious systemic response associ ated with Escherichia coli pneumonia and to determine whether this strategy affected the pulmonary response to tissue infection. Rabbits were pretreat ed,vith either anti-CDI4 mAb or isotype control mAb at 2.5 mg/kg. E. coli ( 1 x 10(9) CFU) was inoculated into the lungs, and the animals were observed for either 4 or 24 h, The blockade of CD14 improved the mean arterial bloo d pressure (p = 0.001) and decreased the i.v. fluid requirements (p = 0.01) . Although this therapy protected the vascular compartment, rabbits treated ,vith anti-CD14 mAb had increased bacterial burdens in the bronchoalveolar lavage fluid recovered from the instilled lung (p = 0.005) and widened alve olar-arterial oxygen difference. Blockade of CD14 prevents the deleterious systemic responses that occur in sepsis; however, other measures are necess ary to control bacterial proliferation at the primary site of infection.