This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sauder, D. N.
Right arrow Articles by Meng, T.-C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sauder, D. N.
Right arrow Articles by Meng, T.-C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2003, p. 3846-3852, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3846-3852.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Randomized, Single-Blind, Placebo-Controlled Study of Topical Application of the Immune Response Modulator Resiquimod in Healthy Adults

Daniel N. Sauder,1,{dagger} Michael H. Smith,2 Therese Senta-McMillian,2 Inmaculada Soria,3 and Tze-Chiang Meng2*

Department of Dermatology, University of Toronto School of Medicine, Toronto, Ontario, Canada,1 Departments of Clinical Research,2 Pharmacokinetics,3M Pharmaceuticals, Saint Paul, Minnesota3

Received 6 May 2003/ Returned for modification 21 July 2003/ Accepted 18 September 2003

Resiquimod is a Toll-like receptor 7 (TLR7) and TLR8 agonist that is a potent inducer of alpha interferon (IFN-{alpha}) and other cytokines. The effects of multiple applications of resiquimod gel were assessed in a randomized, single-blind, dose-ranging, placebo-controlled study with 41 healthy subjects. Over a 3-week period, 1-g doses of resiquimod or vehicle gel (3:1 randomization) were applied to a 50-cm2 area of the upper arm according to the following regimens: 0.25% applied for 8 h two times per week, 0.05% applied for 8 h two times per week, 0.05% applied for 8 h three times per week, and 0.01% applied for 24 h three times per week. Skin biopsy specimens were obtained prior to the application of the first dose and after the completion of application of the last dose. Dosing with 0.01 and 0.05% resiquimod was well tolerated, but that with 0.25% was not; a dose-response relationship for local adverse effects was observed. The level of systemic exposure during multiple topical dosings was <1% of the applied dose. A significant increase in responders after completion of application of the last dose was observed for serum IFN and the interleukin-1 (IL-1) receptor antagonist (P < 0.01, Fisher's exact test). Increased levels of mRNA for IL-6, IL-8, IFN-{alpha}, and Mx (an IFN-{alpha}-inducible protein) were seen in posttreatment biopsy specimens from the group receiving 0.25% resiquimod compared to the levels seen in specimens from the group receiving vehicle only (P < 0.01, Wilcoxon rank sum test). A dose-response-related increase in CD3-positive cells consistent with T-lymphocyte infiltration and a decrease in CD1a-positive cells, consistent with emigration of Langerhans' cells, were observed in treated skin. This study suggests that resiquimod is a potent topically active immune response modifier that significantly enhances the cutaneous immune response.

* Corresponding author. Mailing address: 3M Pharmaceuticals, 3M Center, 275-2W-14, Saint Paul, MN 55144-1000. Phone: (651) 733-1172. Fax: (651) 736-3360. E-mail: tmeng1{at}mmm.com.

{dagger} Present address: Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Md.

Antimicrobial Agents and Chemotherapy, December 2003, p. 3846-3852, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3846-3852.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Smits, E. L. J. M., Ponsaerts, P., Berneman, Z. N., Van Tendeloo, V. F. I. (2008). The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy. The Oncologist 13: 859-875 [Abstract] [Full Text]  
  • Adams, S., O'Neill, D. W., Nonaka, D., Hardin, E., Chiriboga, L., Siu, K., Cruz, C. M., Angiulli, A., Angiulli, F., Ritter, E., Holman, R. M., Shapiro, R. L., Berman, R. S., Berner, N., Shao, Y., Manches, O., Pan, L., Venhaus, R. R., Hoffman, E. W., Jungbluth, A., Gnjatic, S., Old, L., Pavlick, A. C., Bhardwaj, N. (2008). Immunization of Malignant Melanoma Patients with Full-Length NY-ESO-1 Protein Using TLR7 Agonist Imiquimod as Vaccine Adjuvant. J. Immunol. 181: 776-784 [Abstract] [Full Text]  
  • Fife, K. H., Meng, T.-C., Ferris, D. G., Liu, P. (2008). Effect of Resiquimod 0.01% Gel on Lesion Healing and Viral Shedding When Applied to Genital Herpes Lesions. Antimicrob. Agents Chemother. 52: 477-482 [Abstract] [Full Text]  
  • Dummer, R., Hauschild, A., Becker, J. C., Grob, J.-J., Schadendorf, D., Tebbs, V., Skalsky, J., Kaehler, K. C., Moosbauer, S., Clark, R., Meng, T.-C., Urosevic, M. (2008). An Exploratory Study of Systemic Administration of the Toll-like Receptor-7 Agonist 852A in Patients with Refractory Metastatic Melanoma. Clin. Cancer Res. 14: 856-864 [Abstract] [Full Text]  
  • Assier, E., Marin-Esteban, V., Haziot, A., Maggi, E., Charron, D., Mooney, N. (2007). TLR7/8 agonists impair monocyte-derived dendritic cell differentiation and maturation. J. Leukoc. Biol. 81: 221-228 [Abstract] [Full Text]  
  • Pawar, R. D., Patole, P. S., Wornle, M., Anders, H.-J. (2006). Microbial nucleic acids pay a Toll in kidney disease. Am. J. Physiol. Renal Physiol. 291: F509-F516 [Abstract] [Full Text]  
  • Gunzer, M., Riemann, H., Basoglu, Y., Hillmer, A., Weishaupt, C., Balkow, S., Benninghoff, B., Ernst, B., Steinert, M., Scholzen, T., Sunderkotter, C., Grabbe, S. (2005). Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral-blood leukocyte depletion. Blood 106: 2424-2432 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»