PubMed HealthSearch

PubMed · 8503569

Detection of GM-CSF in asthmatic bronchial epithelium and decrease by inhaled corticosteroids.

Abstract

The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in airway epithelial cells in vivo was assessed in 15 asthmatic and 9 normal subjects. GM-CSF was analyzed using immunohistochemistry with a polyclonal and a monoclonal antibody. Hue saturation intensity color image analysis was used to quantify staining. Asthmatic airway epithelial cells stained significantly more with anti-GM-CSF than those from normal subjects (p = 0.0013 and p = 0.0003 for the polyclonal and monoclonal antibodies, respectively). Additionally, 8 asthmatic individuals inhaled 1,000 micrograms beclomethasone diproprionate per day for 8 wk and 6 asthmatic patients inhaled matching placebo. There was a significant reduction of GM-CSF in the epithelium in the patients who were given corticosteroids (p = 0.014), whereas the group of subjects who were given placebo showed no significant change in GM-CSF staining. There was a correlation between the percentage suppression of GM-CSF staining by inhaled corticosteroids and the percentage increase in FEV1 (r = 0.61, p < 0.05) and percentage decrease in carbachol responsiveness (r = 0.80, p < 0.01). These findings suggest that GM-CSF may play a role in the inflammatory processes of bronchial asthma and that the epithelial cell may be a target cell for drug action.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A R Sousa, R N Poston, S J Lane, J A Nakhosteen, T H Lee. 1993. Detection of GM-CSF in asthmatic bronchial epithelium and decrease by inhaled corticosteroids.. https://doi.org/10.1164/ajrccm%2F147.6_pt_1.1557

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Confounding by indication and channeling over time: the risks of beta 2-agonists.

A previously published nested case-control study, the Saskatchewan Asthma Epidemiologic Project (SAEP) spanning 1980-1987, investigated the risk of fatal or near fatal asthma and found different risks for two inhaled beta 2-agonists, fenoterol and salbutamol. The authors assessed whether this comparison was confounded by indication because of channeling of inhaled fenoterol to more severely afflicted asthmatics. Using three subcohorts selected from a cohort of 12,301 asthmatics assembled from the computerized databases of Saskatchewan Health and followed over 7 years, the authors studied two forms of channeling and investigated whether greater asthma severity and less well-controlled disease were associated with preferential prescribing of a first prescription of inhaled fenoterol, as opposed to inhaled salbutamol, and whether they were associated with the likelihood of a switch from inhaled salbutamol to fenoterol as well as a switch from inhaled fenoterol to salbutamol. The authors found that the initial choice between fenoterol and salbutamol was independent of the severity of the asthma and disease control, but that preferential prescribing of fenoterol occurred among users of salbutamol who showed signs of increased severity or uncontrolled asthma. The switch from inhaled fenoterol to salbutamol was, however, minimally related to asthma severity. They conclude that the comparison between inhaled fenoterol and salbutamol in the SAEP may have been biased by indication. This study demonstrates that long-term information on medication use is essential to ensure that the results of such case-control studies are not biased by indication.

Administration, Inhalation

Pharmacological potency and biodisposition of phencyclidine via inhalation exposure in mice.

The purpose of the present study was to characterize the pharmacological effects and biodisposition of phencyclidine (PCP) following inhalation exposure to mice. Results from these studies indicate that PCP was easily volatilized when heated in a glass pipe. Volatilization was efficient with no significant formation of pyrolytic products. Exposure to the volatilized PCP resulted in a dose-dependent impairment in motor performance in both the rotorod and inverted-screen tests. PCP was equally effective in disrupting performance on the inverted-screen and rotorod with ED50 values corresponding to the volatilization of 10.7 and 13.2 mumol, respectively. The time courses were comparable to those produced following intravenous (i.v.) administration of PCP. In order to determine the dose of drug absorbed by inhalation, mice were exposed to [3H]-PCP. The ED50 values of PCP following i.v. administration were 4.1 and 6.2 mumol/kg in the inverted screen and rotorod, respectively. The biodisposition of PCP following inhalation exposure was similar to that after i.v. injections. At doses that produced approximately 50% of the maximum motor impairment by either administration route, higher ratios of the total drug equivalents were found following i.v. injection than that after inhalation, with the brain/plasma ratios of 1.3 +/- 0.2 versus 0.58 +/- 0.02, and brain/body ratios 0.59 +/- 0.06 versus 0.35 +/- 0.1 for i.v. and inhalation, respectively. However, the brain/plasma ratios of the concentrations of PCP were similar, 1.1 versus 0.9. The body concentration of PCP equivalents that produced 50% of the maximum effect after inhalation was 4.7 +/- 0.6 mumol/kg. These results indicate that inhalation of PCP produces a similar pharmacological profile to that of i.v. administration and suggest that the drug is equipotent by these two administrations routes. Moreover, these findings are consistent with the observation that smoking is becoming the most common route of administration among drug users.

Administration, Inhalation