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Environ Health Perspect. 1997 September; 105(Suppl 5): 1265–1271.
PMCID: PMC1470170
Research Article

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-alpha), 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-alpha 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-alpha, compared to unexposed controls, were observed in several particle-exposed groups. Thus, it appears that increased BAL MIP-2 protein levels, but not TNF-alpha, correlate well with the inflammatory response, as measured by PMN numbers in lavaged cells, for both exposure systems.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Brain JD, Knudson DE, Sorokin SP, Davis MA. Pulmonary distribution of particles given by intratracheal instillation or by aerosol inhalation. Environ Res. 1976 Feb;11(1):13–33. [PubMed]
  • Dorries AM, Valberg PA. Heterogeneity of phagocytosis for inhaled versus instilled material. Am Rev Respir Dis. 1992 Oct;146(4):831–837. [PubMed]
  • Pritchard JN, Holmes A, Evans JC, Evans N, Evans RJ, Morgan A. The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillation. Environ Res. 1985 Apr;36(2):268–297. [PubMed]
  • Henderson RF, Driscoll KE, Harkema JR, Lindenschmidt RC, Chang IY, Maples KR, Barr EB. A comparison of the inflammatory response of the lung to inhaled versus instilled particles in F344 rats. Fundam Appl Toxicol. 1995 Feb;24(2):183–197. [PubMed]
  • Oberdörster G, Cox C, Gelein R. Intratracheal instillation versus intratracheal-inhalation of tracer particles for measuring lung clearance function. Exp Lung Res. 1997 Jan-Feb;23(1):17–34. [PubMed]
  • Wolpe SD, Cerami A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 1989 Dec;3(14):2565–2573. [PubMed]
  • Driscoll KE, Hassenbein DG, Howard BW, Isfort RJ, Cody D, Tindal MH, Suchanek M, Carter JM. Cloning, expression, and functional characterization of rat MIP-2: a neutrophil chemoattractant and epithelial cell mitogen. J Leukoc Biol. 1995 Sep;58(3):359–364. [PubMed]
  • Xing Z, Jordana M, Kirpalani H, Driscoll KE, Schall TJ, Gauldie J. Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-alpha, macrophage inflammatory protein-2, interleukin-1 beta, and interleukin-6 but not RANTES or transforming growth factor-beta 1 mRNA expression in acute lung inflammation. Am J Respir Cell Mol Biol. 1994 Feb;10(2):148–153. [PubMed]
  • Greenberger MJ, Strieter RM, Kunkel SL, Danforth JM, Laichalk LL, McGillicuddy DC, Standiford TJ. Neutralization of macrophage inflammatory protein-2 attenuates neutrophil recruitment and bacterial clearance in murine Klebsiella pneumonia. J Infect Dis. 1996 Jan;173(1):159–165. [PubMed]
  • Driscoll KE, Maurer JK. Cytokine and growth factor release by alveolar macrophages: potential biomarkers of pulmonary toxicity. Toxicol Pathol. 1991;19(4 Pt 1):398–405. [PubMed]
  • Lukacs NW, Strieter RM, Chensue SW, Widmer M, Kunkel SL. TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation. J Immunol. 1995 May 15;154(10):5411–5417. [PubMed]
  • Piguet PF, Collart MA, Grau GE, Sappino AP, Vassalli P. Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis. Nature. 1990 Mar 15;344(6263):245–247. [PubMed]
  • Xing Z, Kirpalani H, Torry D, Jordana M, Gauldie J. Polymorphonuclear leukocytes as a significant source of tumor necrosis factor-alpha in endotoxin-challenged lung tissue. Am J Pathol. 1993 Oct;143(4):1009–1015. [PubMed]
  • Warren JS, Barton PA. In vitro analysis of pulmonary inflammation using rat lung organ cultures. Exp Lung Res. 1992 Jan-Mar;18(1):55–67. [PubMed]
  • Oberdörster G, Ferin J, Gelein R, Soderholm SC, Finkelstein J. Role of the alveolar macrophage in lung injury: studies with ultrafine particles. Environ Health Perspect. 1992 Jul;97:193–199. [PMC free article] [PubMed]
  • de Rochemonteix-Galve B, Marchat-Amoruso B, Dayer JM, Rylander R. Tumor necrosis factor and interleukin-1 activities in free lung cells after single and repeated inhalation of bacterial endotoxin. Infect Immun. 1991 Oct;59(10):3646–3650. [PMC free article] [PubMed]
  • Henderson RF, Barr EB, Cheng YS, Griffith WC, Hahn FF. The effect of exposure pattern on the accumulation of particles and the response of the lung to inhaled particles. Fundam Appl Toxicol. 1992 Oct;19(3):367–374. [PubMed]

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