Modulation of rat bronchoalveolar lavage cell function by the intratracheal delivery of interferon-gamma.

Abstract

To determine if there is a rationale for compartmentalized immunostimulation, we have carried out a series of experiments to evaluate whether intratracheal delivery of interferon-gamma (rRatIFN-gamma) can activate rat bronchoalveolar lavage cells (BAL) for in vitro expression of tumoricidal activity against xenogeneic P815 tumor cells and enhanced in vitro microbicidal activity against the intracellular protozoan Toxoplasma gondii. Treatment of rat alveolar macrophages in vitro activates them for both of these activities as well as enhanced production of superoxide anion. We found that a single intratracheal dose of 5,000-10,000 units of rRatIFN-gamma activated rat BAL for both microbicidal and tumoricidal activity. To determine the duration of activation, microbicidal activity was determined 1, 2, 3, 5, and 7 days after a single intratracheal dose of 5,000 units of IFN. Enhanced microbicidal activity was maintained through day 3 but returned to control levels by day 5. Alveolar macrophages always accounted for the majority of cells in the lavage populations. However, intratracheal IFN caused an increase in the number of polymorphonuclear leukocytes and lymphocytes in the lavageable cells and, although these cells were always in the minority, they may have contributed to both the tumoricidal and microbicidal activity of the lavage cells. These studies demonstrate that local administration of an immunostimulant can activate pulmonary defense cells and may be a feasible route of drug delivery for prophylaxis against pulmonary infections.