Intratracheal instillation versus intratracheal inhalation: influence of cytokines on inflammatory response.

Abstract

Our laboratory has developed a method of particle exposure whereby anesthetized rats intratracheally inhale, at a regulated breathing rate and pressure, an aerosolized test material. This method is capable of delivering considerable doses in a short time period and, unlike the commonly used method of intratracheal instillation, does so with an even particle distribution throughout the lung. Early studies comparing the response of male Fischer 344 rats exposed to TiO2 particles of two differing primary particle sizes showed that at similar particle doses animals exposed by the two methods showed differences in response, as measured by bronchoalveolar lavage (BAL) parameters. Building on this, we sought to study the roles that macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor alpha (TNF-a), two cytokines thought to have proinflammatory roles in the lung, may play in the differences observed. Increases in MIP-2 protein levels in the lavaged cells, but not the supernatant, were observed in those groups where increased polymorphonuclear cells (PMN) in the lung lavage were found, but not in those where no increase in PMN levels was observed. BAL TNF-a levels, measured by enzyme-linked immunosorbent assay, showed no apparent correlation with cellular or biochemical BAL parameters for either particle size or dosing method. Increases in immunocytochemical staining for TNF-a, compared to unexposed controls, were observed in several particle-exposed groups. Thus, it appears that increased BAL MIP-2 protein levels, but not TNF-a, correlate well with the inflammatory response, as measured by PMN numbers in lavaged cells, for both exposure systems. Environ Health Perspect 1 05(Suppl 5):1 265-1271 (1997)

Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines.

“…Silicon dioxide can cause serious lung disease, but at much higher, occupational concentrations than found in the CAPs samples in this study (41). Aluminum is generally not considered an airborne hazard; likewise, titanium-rich particle concentrations far higher than those observed in the present study are considered necessary to induce biologic responses (42,43). Indeed, titanium dioxide is often used as a negative control in studies investigating particle inhalation effects.…”

Murine Aerosol Challenge Model of Anthrax

“…Different pulmonary administration routes (i.t and i.n. versus aerosol exposure) can vary the course or kinetics of the host response, subsequently altering disease pathogenesis (31,32,42). As pulmonary anthrax after exposure to spore aerosols is the most likely route of infection to be used in any future biowarfare or bioterrorist attack, the aerosol delivery system is preferred for modeling inhalational anthrax and studying host pathogen interactions.…”

Nanosafety Research—Are We on the Right Track?

“…A comprehensive comparison of the two methods was made more than 15 years ago by a group led by Oberdçrster. [74][75][76] A clear description of instillation and its limitations in association with the investigation of aerosols was published in 2000. [77] One might be justified in assuming that these results have become accepted by those performing experiments on nanomaterials and expect that such studies would now be designed in accordance with these established rules.…”