Abstract
Objective: We postulated that either oral or vaginal administration of the immune response modifier imiquimod would decrease vaginal shedding of Chlamydia trachomatis, mouse pneumonitis strain (MoPn), in a murine model.
Methods: Female BALB/c mice were infected intravaginally withC. trachomatis (MoPn) and were administered imiquimod either orally (30 mg/kg) or vaginally (10 μl of 5%imiquimod cream) prior to infection and every second day after infection for a total of four doses. The course of infection was monitored by collecting cervical–vaginal swabs and isolation in HeLa 229 cell culture. To determine whether the drug affected T helper type 1 or T helper type 2 immune response polarization, immunoglobulinG(IgG) subclass antibody responses were assessed at day 56 after infection.
Results: There was no significant difference in the course of infection when imiquimod-treated mice were compared with sham-treated controls, regardless of whether the drug was administered orally or vaginally. IgG subclass antibody responses, and by extension, T helper type 1 to T helper type 2 immune response polarization, were also unaffected.
Conclusions: Imiquimod has no efficacy in controllingC. trachomatis (MoPn) infection in the murine model.
Full Text
The Full Text of this article is available as a PDF (335.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arevalo I., Ward B., Miller R., Meng T. C., Najar E., Alvarez E., Matlashewski G., Llanos-Cuentas A. Successful treatment of drug-resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clin Infect Dis. 2001 Oct 23;33(11):1847–1851. doi: 10.1086/324161. [DOI] [PubMed] [Google Scholar]
- Beatty W. L., Morrison R. P., Byrne G. I. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev. 1994 Dec;58(4):686–699. doi: 10.1128/mr.58.4.686-699.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernstein D. I., Harrison C. J. Effects of the immunomodulating agent R837 on acute and latent herpes simplex virus type 2 infections. Antimicrob Agents Chemother. 1989 Sep;33(9):1511–1515. doi: 10.1128/aac.33.9.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buates S., Matlashewski G. Treatment of experimental leishmaniasis with the immunomodulators imiquimod and S-28463: efficacy and mode of action. J Infect Dis. 1999 Jun;179(6):1485–1494. doi: 10.1086/314782. [DOI] [PubMed] [Google Scholar]
- Chen M., Griffith B. P., Lucia H. L., Hsiung G. D. Efficacy of S26308 against guinea pig cytomegalovirus infection. Antimicrob Agents Chemother. 1988 May;32(5):678–683. doi: 10.1128/aac.32.5.678. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cotter T. W., Meng Q., Shen Z. L., Zhang Y. X., Su H., Caldwell H. D. Protective efficacy of major outer membrane protein-specific immunoglobulin A (IgA) and IgG monoclonal antibodies in a murine model of Chlamydia trachomatis genital tract infection. Infect Immun. 1995 Dec;63(12):4704–4714. doi: 10.1128/iai.63.12.4704-4714.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cotter T. W., Ramsey K. H., Miranpuri G. S., Poulsen C. E., Byrne G. I. Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice. Infect Immun. 1997 Jun;65(6):2145–2152. doi: 10.1128/iai.65.6.2145-2152.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dockrell D. H., Kinghorn G. R. Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother. 2001 Dec;48(6):751–755. doi: 10.1093/jac/48.6.751. [DOI] [PubMed] [Google Scholar]
- Gilbert J., Drehs M. M., Weinberg J. M. Topical imiquimod for acyclovir-unresponsive herpes simplex virus 2 infection. Arch Dermatol. 2001 Aug;137(8):1015–1017. [PubMed] [Google Scholar]
- Gupta Aditya K., Browne Melanie, Bluhm Robyn. Imiquimod: a review. J Cutan Med Surg. 2002 Oct 9;6(6):554–560. doi: 10.1007/s10227-001-0134-6. [DOI] [PubMed] [Google Scholar]
- Harrison C. J., Jenski L., Voychehovski T., Bernstein D. I. Modification of immunological responses and clinical disease during topical R-837 treatment of genital HSV-2 infection. Antiviral Res. 1988 Dec 1;10(4-5):209–223. doi: 10.1016/0166-3542(88)90032-0. [DOI] [PubMed] [Google Scholar]
- Harrison C. J., Miller R. L., Bernstein D. I. Posttherapy suppression of genital herpes simplex virus (HSV) recurrences and enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs. Antimicrob Agents Chemother. 1994 Sep;38(9):2059–2064. doi: 10.1128/aac.38.9.2059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harrison C. J., Stanberry L. R., Bernstein D. I. Effects of cytokines and R-837, a cytokine inducer, on UV-irradiation augmented recurrent genital herpes in guinea pigs. Antiviral Res. 1991 May;15(4):315–322. doi: 10.1016/0166-3542(91)90012-g. [DOI] [PubMed] [Google Scholar]
- Hemmi Hiroaki, Kaisho Tsuneyasu, Takeuchi Osamu, Sato Shintaro, Sanjo Hideki, Hoshino Katsuaki, Horiuchi Takao, Tomizawa Hideyuki, Takeda Kiyoshi, Akira Shizuo. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002 Jan 22;3(2):196–200. doi: 10.1038/ni758. [DOI] [PubMed] [Google Scholar]
- Hengge U. R., Benninghoff B., Ruzicka T., Goos M. Topical immunomodulators--progress towards treating inflammation, infection, and cancer. Lancet Infect Dis. 2001 Oct;1(3):189–198. doi: 10.1016/s1473-3099(01)00095-0. [DOI] [PubMed] [Google Scholar]
- Hengge U. R., Esser S., Schultewolter T., Behrendt C., Meyer T., Stockfleth E., Goos M. Self-administered topical 5% imiquimod for the treatment of common warts and molluscum contagiosum. Br J Dermatol. 2000 Nov;143(5):1026–1031. doi: 10.1046/j.1365-2133.2000.03777.x. [DOI] [PubMed] [Google Scholar]
- Hengge U. R., Goos M., Arndt R. Topical treatment of warts and mollusca with imiquimod. Ann Intern Med. 2000 Jan 4;132(1):95–95. doi: 10.7326/0003-4819-132-1-200001040-00024. [DOI] [PubMed] [Google Scholar]
- Igietseme J. U., Ramsey K. H., Magee D. M., Williams D. M., Kincy T. J., Rank R. G. Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone. Reg Immunol. 1993 Nov-Dec;5(6):317–324. [PubMed] [Google Scholar]
- Kelly K. A., Rank R. G. Identification of homing receptors that mediate the recruitment of CD4 T cells to the genital tract following intravaginal infection with Chlamydia trachomatis. Infect Immun. 1997 Dec;65(12):5198–5208. doi: 10.1128/iai.65.12.5198-5208.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly K. A., Robinson E. A., Rank R. G. Initial route of antigen administration alters the T-cell cytokine profile produced in response to the mouse pneumonitis biovar of Chlamydia trachomatis following genital infection. Infect Immun. 1996 Dec;64(12):4976–4983. doi: 10.1128/iai.64.12.4976-4983.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore Terri, Ananaba Godwin A., Bolier Jacqueline, Bowers Samera, Belay Tesfaye, Eko Francis O., Igietseme Joseph U. Fc receptor regulation of protective immunity against Chlamydia trachomatis. Immunology. 2002 Feb;105(2):213–221. doi: 10.1046/j.0019-2805.2001.01354.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morrison S. G., Su H., Caldwell H. D., Morrison R. P. Immunity to murine Chlamydia trachomatis genital tract reinfection involves B cells and CD4(+) T cells but not CD8(+) T cells. Infect Immun. 2000 Dec;68(12):6979–6987. doi: 10.1128/iai.68.12.6979-6987.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsey K. H., Miranpuri G. S., Sigar I. M., Ouellette S., Byrne G. I. Chlamydia trachomatis persistence in the female mouse genital tract: inducible nitric oxide synthase and infection outcome. Infect Immun. 2001 Aug;69(8):5131–5137. doi: 10.1128/IAI.69.8.5131-5137.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsey K. H., Newhall W. J., 5th, Rank R. G. Humoral immune response to chlamydial genital infection of mice with the agent of mouse pneumonitis. Infect Immun. 1989 Aug;57(8):2441–2446. doi: 10.1128/iai.57.8.2441-2446.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsey K. H., Rank R. G. Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines. Infect Immun. 1991 Mar;59(3):925–931. doi: 10.1128/iai.59.3.925-931.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsey K. H., Sigar I. M., Rana S. V., Gupta J., Holland S. M., Byrne G. I. Role for inducible nitric oxide synthase in protection from chronic Chlamydia trachomatis urogenital disease in mice and its regulation by oxygen free radicals. Infect Immun. 2001 Dec;69(12):7374–7379. doi: 10.1128/IAI.69.12.7374-7379.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsey K. H., Soderberg L. S., Rank R. G. Resolution of chlamydial genital infection in B-cell-deficient mice and immunity to reinfection. Infect Immun. 1988 May;56(5):1320–1325. doi: 10.1128/iai.56.5.1320-1325.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank R. G., Ramsey K. H., Pack E. A., Williams D. M. Effect of gamma interferon on resolution of murine chlamydial genital infection. Infect Immun. 1992 Oct;60(10):4427–4429. doi: 10.1128/iai.60.10.4427-4429.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank R. G., Soderberg L. S., Barron A. L. Chronic chlamydial genital infection in congenitally athymic nude mice. Infect Immun. 1985 Jun;48(3):847–849. doi: 10.1128/iai.48.3.847-849.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sauder D. N. Immunomodulatory and pharmacologic properties of imiquimod. J Am Acad Dermatol. 2000 Jul;43(1 Pt 2):S6–11. doi: 10.1067/mjd.2000.107808. [DOI] [PubMed] [Google Scholar]
- Snapper C. M., Paul W. E. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. doi: 10.1126/science.3107127. [DOI] [PubMed] [Google Scholar]
- Su H., Messer R., Whitmire W., Fischer E., Portis J. C., Caldwell H. D. Vaccination against chlamydial genital tract infection after immunization with dendritic cells pulsed ex vivo with nonviable Chlamydiae. J Exp Med. 1998 Sep 7;188(5):809–818. doi: 10.1084/jem.188.5.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de la Maza L. M., Pal S., Khamesipour A., Peterson E. M. Intravaginal inoculation of mice with the Chlamydia trachomatis mouse pneumonitis biovar results in infertility. Infect Immun. 1994 May;62(5):2094–2097. doi: 10.1128/iai.62.5.2094-2097.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]