PMID- 12748037
OWN - NLM
STAT- MEDLINE
DCOM- 20030708
LR  - 20201208
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 188
IP  - 1
DP  - 2003 Jun 3
TI  - Impact of exposure duration by low molecular weight compounds on interferon-gamma 
      and interleukin-4 mRNA expression and production in the draining lymph nodes of 
      mice.
PG  - 1-13
AB  - The local lymph node assay (LLNA) is used to identify allergens by means of 
      dermal exposure. For hazard identification, besides identification also the 
      distinction between contact and respiratory allergens is of importance. We have 
      previously shown that a modified LLNA can be used to identify respiratory 
      allergens, on the basis of Con A induced IL-4 production. Here we show a good 
      qualitative correlation between mRNA expression and production of IFN-gamma and 
      IL-4. This suggests that distinction between contact and respiratory allergens 
      may also be studied at the mRNA expression level. Secondly, another assay, 
      similar to the modified LLNA but differing in the duration and the number of 
      allergen applications as well as in the ex vivo culture conditions, here denoted 
      as 'longer' assay, has been reported to be able to identify contact allergens, on 
      the basis of (spontaneous) IFN-gamma production. In the present study we have 
      compared these assays. Similar to our previous findings, in the modified LLNA 
      exposure to the respiratory allergen trimellitic anhydride (TMA) resulted in a 
      approximately 10-fold higher Con A induced IL-4 production compared with the 
      contact allergen dinitrochlorobenzene (DNCB), while exposure to both allergens 
      resulted in a similar Con A induced IFN-gamma production. In the 'longer' assay, 
      TMA exposure resulted in Con A induced IL-4 production whereas DNCB exposure did 
      not. Importantly, only a 2-fold higher spontaneous IFN-gamma production was 
      induced by DNCB compared with TMA, the difference being not statistically 
      significant. Thus, although the 'longer' assay indeed showed a somewhat higher 
      IFN-gamma induction by DNCB compared with TMA, the magnitude and robustness of 
      this effect question its applicability. These results favor the modified LLNA 
      since it is shorter, and combines identification of allergens (by cell 
      proliferation) with identification of respiratory allergens (by IL-4 production). 
      Compounds that induce cell proliferation with a low concomitant IL-4 production 
      may thus be identified as contact allergens, although the need to positively 
      identity such allergens remain.
FAU - Vandebriel, Rob J
AU  - Vandebriel RJ
AD  - Laboratory for Pathology and Immunobiology, National Institute of Public Health 
      and the Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands. 
      r.vandebriel@rivm.nl
FAU - De Jong, Wim H
AU  - De Jong WH
FAU - Hendriks, Jerome J A
AU  - Hendriks JJ
FAU - Van Loveren, Henk
AU  - Van Loveren H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Allergens)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Phthalic Anhydrides)
RN  - 0 (RNA, Messenger)
RN  - 11028-71-0 (Concanavalin A)
RN  - 207137-56-2 (Interleukin-4)
RN  - 80T61EUU7H (trimellitic anhydride)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Allergens/*toxicity
MH  - Animals
MH  - Concanavalin A/pharmacology
MH  - Dinitrochlorobenzene/*toxicity
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Hypersensitivity/etiology/immunology
MH  - Interferon-gamma/biosynthesis/*genetics
MH  - Interleukin-4/biosynthesis/*genetics
MH  - *Local Lymph Node Assay
MH  - Lymph Nodes/*drug effects/immunology/metabolism
MH  - Lymphocyte Activation
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phthalic Anhydrides/*toxicity
MH  - RNA, Messenger/*biosynthesis/chemistry/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2003/05/16 05:00
MHDA- 2003/07/09 05:00
CRDT- 2003/05/16 05:00
PHST- 2003/05/16 05:00 [pubmed]
PHST- 2003/07/09 05:00 [medline]
PHST- 2003/05/16 05:00 [entrez]
AID - S0300483X02007424 [pii]
AID - 10.1016/s0300-483x(02)00742-4 [doi]
PST - ppublish
SO  - Toxicology. 2003 Jun 3;188(1):1-13. doi: 10.1016/s0300-483x(02)00742-4.