PMID- 22913509
OWN - NLM
STAT- MEDLINE
DCOM- 20130128
LR  - 20131121
IS  - 1398-9995 (Electronic)
IS  - 0105-4538 (Linking)
VI  - 67
IP  - 10
DP  - 2012 Oct
TI  - Preventive and therapeutic effects of rapamycin, a mammalian target of rapamycin 
      inhibitor, on food allergy in mice.
PG  - 1259-70
LID - 10.1111/all.12000 [doi]
AB  - BACKGROUND: Because few curative treatments are available for food allergy, we 
      investigated the therapeutic potential of rapamycin, a mammalian target of 
      rapamycin (mTOR) inhibitor, on mouse food allergy. METHODS: The preventive and 
      therapeutic effects of oral rapamycin on anaphylactic symptoms induced by oral 
      ovalbumin (OVA) challenge in food allergy mice were investigated. Mast cell 
      functions in response to rapamycin were also measured in the passive systemic 
      anaphylaxis model and bone marrow-derived mast cells (BMMCs). RESULTS: Daily 
      rapamycin from the first challenge (preventive protocol) attenuated food allergy 
      symptoms including diarrhea, anaphylactic reactions, and hypothermia in mice. The 
      treatment decreased the challenge-induced increases in mouse mast cell protease-1 
      in serum and mast cell numbers in the intestine. Notably, the mice that already 
      showed food allergy symptoms by previous challenges recovered from the disease 
      with daily administration of rapamycin (therapeutic protocol). Anti-OVA IgG1 and 
      IgE levels in serum, as well as IFN-gamma, IL-4, IL-13, IL-9, IL-10, and IL-17 
      secretion from splenocytes, were decreased by the treatments. In contrast, a 
      single dose of rapamycin failed to affect passive systemic anaphylaxis. 
      Spontaneous and IL-9-dependent survival and IgE-induced IL-13 secretion, but not 
      degranulation, of BMMCs were reduced by rapamycin. CONCLUSION: Our data show that 
      mouse food allergy was attenuated by rapamycin through an immunosuppressive 
      effect and inhibition of intestinal mast cell hyperplasia. Inhibition of the IL-9 
      production-mast cell survival axis is one of the mechanisms of the therapeutic 
      effect of rapamycin. Rapamycin and other mTOR inhibitors might be good candidates 
      for therapeutic drugs for food allergy.
CI  - (c) 2012 John Wiley & Sons A/S.
FAU - Yamaki, K
AU  - Yamaki K
AD  - Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Hyogo, Japan. 
      yam@kobepharma-u.ac.jp
FAU - Yoshino, S
AU  - Yoshino S
LA  - eng
PT  - Journal Article
DEP - 20120823
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (Immunosuppressive Agents)
RN  - 9006-59-1 (Ovalbumin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Administration, Oral
MH  - Anaphylaxis/drug therapy/prevention & control
MH  - Animals
MH  - Food Hypersensitivity/*drug therapy/*prevention & control
MH  - Immunosuppressive Agents/administration & dosage/*therapeutic use
MH  - Male
MH  - Mast Cells/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Ovalbumin/administration & dosage/adverse effects/immunology
MH  - Sirolimus/administration & dosage/*therapeutic use
MH  - Treatment Outcome
EDAT- 2012/08/24 06:00
MHDA- 2013/01/29 06:00
CRDT- 2012/08/24 06:00
PHST- 2012/07/11 00:00 [accepted]
PHST- 2012/08/24 06:00 [entrez]
PHST- 2012/08/24 06:00 [pubmed]
PHST- 2013/01/29 06:00 [medline]
AID - 10.1111/all.12000 [doi]
PST - ppublish
SO  - Allergy. 2012 Oct;67(10):1259-70. doi: 10.1111/all.12000. Epub 2012 Aug 23.