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. 1992 Nov;47(11):948–951. doi: 10.1136/thx.47.11.948

Failure of salmeterol to inhibit circulating white cell responses and bronchoconstriction induced by platelet activating factor.

J Spring 1, S R Johnston 1, J Seale 1, P W Ind 1
PMCID: PMC464105  PMID: 1361250

Abstract

BACKGROUND: Platelet activating factor (PAF) is a potent mediator of inflammation. Inhalation of PAF causes acute bronchoconstriction and a transient fall in white blood cell count in humans. Salmeterol inhibits pulmonary inflammation induced by PAF in guinea pigs. METHODS: The effect of salmeterol on effects induced by PAF was investigated in eight normal subjects who inhaled salmeterol (50 micrograms) twice daily or a matched placebo for one week before challenge with PAF. Blood samples were taken from a forearm catheter for total white cell and neutrophil counts before and for 30 minutes after administration of PAF (48 micrograms) through a Mefar dosimeter. Blood films were stained for unsegmented neutrophils before and after treatment with PAF on a placebo day. RESULTS: Mean baseline total white cell counts and neutrophil counts did not differ on the two days. Mean baseline sGaw was significantly higher after inhaled salmeterol (1.84 (95% C1 1.45-2.23) s-1kPa-1) than after placebo (1.53 (1.24-1.82)). After placebo mean total white cell counts, neutrophil counts, and sGaw were reduced to 60 (43-78)%, 39 (14-64)%, and 82 (71-93)% of baseline respectively five minutes after inhaled PAF. After salmeterol treatment mean reductions five minutes after inhaled PAF were 59 (45-73)%, 40 (19-61)%, and 82 (71-93)% of baseline respectively. At 30 minutes after treatment with PAF the neutrophil count rebounded to 143 (82-204)% of baseline after placebo and to 127 (93-161)% after inhaled salmeterol. There was no significant difference in the percentage of immature neutrophils before and after treatment with PAF (2.0 (0.5-2.6)% compared with 3.9 (2.2-5.6)%. CONCLUSIONS: Treatment with salmeterol did not inhibit reduction in total white cell count or neutrophil count, rebound neutrophilia, acute bronchoconstriction, or transient flushing after inhalation of PAF. These results conflict with the inhibitory effect of salmeterol on lung inflammation in guinea pigs but are consistent with the lack of effect of salbutamol in humans. Salmeterol does not have an anti-PAF effect in vivo in humans.

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Selected References

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  1. Barnes P. J., Chung K. F., Page C. P. Platelet-activating factor as a mediator of allergic disease. J Allergy Clin Immunol. 1988 May;81(5 Pt 1):919–934. doi: 10.1016/0091-6749(88)90952-9. [DOI] [PubMed] [Google Scholar]
  2. Chowienczyk P. J., Rees P. J., Payne J., Clark T. J. A new method for computer-assisted determination of airways resistance. J Appl Physiol Respir Environ Exerc Physiol. 1981 Mar;50(3):672–678. doi: 10.1152/jappl.1981.50.3.672. [DOI] [PubMed] [Google Scholar]
  3. Chung K. F., Dent G., Barnes P. J. Effects of salbutamol on bronchoconstriction, bronchial hyperresponsiveness, and leucocyte responses induced by platelet activating factor in man. Thorax. 1989 Feb;44(2):102–107. doi: 10.1136/thx.44.2.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cuss F. M., Dixon C. M., Barnes P. J. Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancet. 1986 Jul 26;2(8500):189–192. doi: 10.1016/s0140-6736(86)92489-x. [DOI] [PubMed] [Google Scholar]
  5. Jancar S., Thériault P., Lauzière M., Braquet P., Sirois P. Paf-induced release of spasmogens from guinea-pig lungs. Br J Pharmacol. 1989 Jan;96(1):153–162. doi: 10.1111/j.1476-5381.1989.tb11795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lai C. K., Jenkins J. R., Polosa R., Holgate S. T. Inhaled PAF fails to induce airway hyperresponsiveness to methacholine in normal human subjects. J Appl Physiol (1985) 1990 Mar;68(3):919–926. doi: 10.1152/jappl.1990.68.3.919. [DOI] [PubMed] [Google Scholar]
  7. Lammers J. W., Kioumis I., McCusker M., Nichol G. M., Barnes P. J., Chung K. F. Effects of prostacyclin on bronchoconstriction and neutropenia induced by inhaled platelet-activating factor in man. J Allergy Clin Immunol. 1990 Apr;85(4):763–769. doi: 10.1016/0091-6749(90)90196-b. [DOI] [PubMed] [Google Scholar]
  8. Smith L. J., Rubin A. H., Patterson R. Mechanism of platelet activating factor-induced bronchoconstriction in humans. Am Rev Respir Dis. 1988 May;137(5):1015–1019. doi: 10.1164/ajrccm/137.5.1015. [DOI] [PubMed] [Google Scholar]
  9. Spencer D. A., Evans J. M., Green S. E., Piper P. J., Costello J. F. Participation of the cysteinyl leukotrienes in the acute bronchoconstrictor response to inhaled platelet activating factor in man. Thorax. 1991 Jun;46(6):441–445. doi: 10.1136/thx.46.6.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Spencer D. A., Green S. E., Evans J. M., Piper P. J., Costello J. F. Platelet activating factor does not cause a reproducible increase in bronchial responsiveness in normal man. Clin Exp Allergy. 1990 Sep;20(5):525–532. doi: 10.1111/j.1365-2222.1990.tb03145.x. [DOI] [PubMed] [Google Scholar]
  11. Taylor I. K., Ward P. S., Taylor G. W., Dollery C. T., Fuller R. W. Inhaled PAF stimulates leukotriene and thromboxane A2 production in humans. J Appl Physiol (1985) 1991 Oct;71(4):1396–1402. doi: 10.1152/jappl.1991.71.4.1396. [DOI] [PubMed] [Google Scholar]
  12. Toogood J. H. Risk of anaphylaxis in patients receiving beta-blocker drugs. J Allergy Clin Immunol. 1988 Jan;81(1):1–5. doi: 10.1016/0091-6749(88)90212-6. [DOI] [PubMed] [Google Scholar]
  13. Twentyman O. P., Finnerty J. P., Harris A., Palmer J., Holgate S. T. Protection against allergen-induced asthma by salmeterol. Lancet. 1990 Dec 1;336(8727):1338–1342. doi: 10.1016/0140-6736(90)92894-n. [DOI] [PubMed] [Google Scholar]
  14. Wardlaw A. J., Chung K. F., Moqbel R., MacDonald A. J., Hartnell A., McCusker M., Collins J. V., Barnes P. J., Kay A. B. Effects of inhaled PAF in humans on circulating and bronchoalveolar lavage fluid neutrophils. Relationship to bronchoconstriction and changes in airway responsiveness. Am Rev Respir Dis. 1990 Feb;141(2):386–392. doi: 10.1164/ajrccm/141.2.386. [DOI] [PubMed] [Google Scholar]
  15. van Donselaar C. A., Habbema J. D. Recurrence after first seizure. Lancet. 1991 Jan 5;337(8732):46–46. doi: 10.1016/0140-6736(91)93361-c. [DOI] [PubMed] [Google Scholar]

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