Prophylactic therapy with recombinant granulocyte colony stimulating factor (rG-CSF) to augment host defenses may be applicable to critically ill patients requiring mechanical ventilation and oxygen therapy, and at risk of developing nosocomial pneumonia. Because the neutrophil has been implicated both in oxygen toxicity as well as some of the organ injury associated with pneumonia however, rG-CSF therapy in such patients may aggravate neutrophil mediated inflammatory injury, resulting in detrimental rather than beneficial effects. We are performing a series of experiments looking at the effects of stimulating neutrophil number with rG-CSF in normal rats and rats with an intrabronchial bacterial inoculum, exposed to moderate and high concentrations of oxygen. In addition, we are also assessing the effects of inhibiting neutrophil function with monoclonal antibodies directed against the leukocyte CD 11/18 adhesion complex (CD 11/18 MAb), in similar groups of oxygen exposed animals with and without pneumonia. Thus far we have shown that oxygen therapy, even at very high and toxic concentrations, does not produce harmful effects related to rG-CSF pretreatment in normal animals. CD 11/18 MAb therapy does not appear to modify changes associated with oxygen although these findings are preliminary. Disturbingly, however, we are finding that, in contrast to the beneficial effects of rG-CSF pretreatment in our canine model of bacterial peritonitis, similar pretreatment in rats administered intrabronchial bacteria is harmful. It is unclear what the interactions are yet between rG-CSF. This study is still underway. When it is completed we will assess the effects of CD 11/18 inhibition in this model of pneumonia.
