PMID- 15963264
OWN - NLM
STAT- MEDLINE
DCOM- 20050906
LR  - 20200225
IS  - 1582-1838 (Print)
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Linking)
VI  - 9
IP  - 2
DP  - 2005 Apr-Jun
TI  - Immune responses induced by intranasal imiquimod and implications for 
      therapeutics in rhinovirus infections.
PG  - 457-61
AB  - Notwithstanding the progress recently made in immunology and virology, there is 
      yet no effective, specific treatment for the common cold. Symptomatic treatment 
      is minimally effective. An anecdotal report of rapid clearing of the common cold 
      of recent onset after intranasal application of imiquimod in several subjects by 
      one of the authors, made us test the hypothesis that this treatment works through 
      the secretion of interferon by the nasal mucosa. We decided to do an animal study 
      in primates (Indian Macaca Mulata): 5 treatment and 3 control animals were used. 
      Imiquimod or placebo was massaged into the nares of the animals and periodic 
      samples of post-nasal fluid were taken and measurements for Interferon alpha 
      (IFNalpha) and Tumor Necrosis Factor alpha (TNFalpha) were made by ELISA methods, 
      and kinetic studies. mRNA IFNalpha was also isolated and analyzed by quantitative 
      competitive RT-PCR. The internal standard was constructed to be complementary to 
      and compete with oligonucleotide primers and for amplification of target 
      sequences. One intranasal application of imiquimod rapidly (1-4 Hours) induced 
      high levels of mRNA for IFNalpha, and minimal levels in the control animals. 
      Rapid induction of INFalpha, and proportional increase of TNFalpha sustained for 
      4 and 6 hours respectively were noted. No adverse reactions to treatment were 
      found in macaques during this short period of intranasal imiquimod usage (except 
      in one macaque with a short period of lacrimation). No animal had cytotoxic 
      effects when examined at 6 hr, 12 hr, 24 hr or 48 hr, except one animal, which 
      had an episode of lacrimation for 6 hr post treatment. Thus both safety and 
      efficacy of short treatment with imiquimod is proven in this animal model. Proof 
      of principle for intranasal treatment of the common cold with imiquimod is shown. 
      We think that this work will encourage a number of double blind clinical trials 
      to confirm the effectiveness of the intranasal treatment of the common cold with 
      imiquimod.
FAU - Clejan, Sanda
AU  - Clejan S
AD  - Department of Pathology & Laboratory Medicine, Tulane University School of 
      Medicine and the General Clinical Research Center, New Orleans, LA, 70112-2699, 
      USA. sclejan@tulane.edu
FAU - Mandrea, E
AU  - Mandrea E
FAU - Pandrea, Ivona V
AU  - Pandrea IV
FAU - Dufour, J
AU  - Dufour J
FAU - Japa, S
AU  - Japa S
FAU - Veazey, R S
AU  - Veazey RS
LA  - eng
GR  - 5M01 RR05096-01A1/RR/NCRR NIH HHS/United States
GR  - AI51649/AI/NIAID NIH HHS/United States
GR  - RR000164/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Aminoquinolines)
RN  - 0 (Interferon Inducers)
RN  - 0 (Interferon-alpha)
RN  - 0 (Lymphotoxin-alpha)
RN  - 0 (RNA, Messenger)
RN  - P1QW714R7M (Imiquimod)
SB  - IM
MH  - Adjuvants, Immunologic/adverse effects/pharmacology/therapeutic use
MH  - Administration, Intranasal
MH  - Aminoquinolines/adverse effects/*pharmacology/therapeutic use
MH  - Animals
MH  - Common Cold/*drug therapy
MH  - Gene Expression/drug effects
MH  - Imiquimod
MH  - Immunotherapy, Active/*methods
MH  - Interferon Inducers/adverse effects/pharmacology/therapeutic use
MH  - Interferon-alpha/genetics/metabolism
MH  - Lymphotoxin-alpha/metabolism
MH  - Macaca mulatta
MH  - Nasal Mucosa/*drug effects/immunology/metabolism
MH  - RNA, Messenger/genetics/metabolism
PMC - PMC6740272
EDAT- 2005/06/21 09:00
MHDA- 2005/09/07 09:00
PMCR- 2005/04/01
CRDT- 2005/06/21 09:00
PHST- 2005/06/21 09:00 [pubmed]
PHST- 2005/09/07 09:00 [medline]
PHST- 2005/06/21 09:00 [entrez]
PHST- 2005/04/01 00:00 [pmc-release]
AID - 009.002.20 [pii]
AID - JCMM457 [pii]
AID - 10.1111/j.1582-4934.2005.tb00370.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2005 Apr-Jun;9(2):457-61. doi: 
      10.1111/j.1582-4934.2005.tb00370.x.