Abstract
Objectives: Studies of novel immunosuppressive agents using small numbers of healthy volunteers require validated methods for detecting pharmacodynamic effects. We investigated the ability of tuberculin-stimulated lymphocyte proliferation in whole blood and the tuberculin skin test to assess immunosuppression in healthy volunteers.
Methods: This was a parallel-group, placebo-controlled study. Five weeks after a tuberculin test, 14 study participants received either placebo or prednisolone (30mg or 60mg) once daily for 7 days. Blood samples were collected before the first dose and at 2 hours post-first dose for assessment of lymphocyte proliferation. On day 5, a repeat skin test was administered.
Results: Lymphocyte proliferation was reduced in all ten study participants who received prednisolone (mean reduction: 30mg=77.5%, 60mg=77%; p < 0.01 compared with placebo) with no reduction in any of the placebo group. While prednisolone reduced skin test size in seven study participants, there was an increase in three participants and no overall significant effect compared with placebo (p > 0.05).
Conclusion: Lymphocyte proliferation in whole blood was able to detect pharmacological immunosuppression in healthy individuals, while the tuberculin skin test did not. This whole blood method may have applications for detecting the effects of novel compounds in future healthy volunteer studies.
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Acknowledgements
This study was funded entirely by AstraZeneca Pharmaceuticals. During the study, Dave Singh’s salary was paid by AstraZeneca, and George Booth is an employee of AstraZeneca.
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Singh, D., Woodcock, A. & Booth, G. Pharmacodynamic Measurements of Immunosuppression in Healthy Individuals. Int J Pharm Med 17, 131–136 (2003). https://doi.org/10.1097/00124363-200317030-00006
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DOI: https://doi.org/10.1097/00124363-200317030-00006