PMID- 10637130
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20201208
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 162
IP  - 2
DP  - 2000 Jan 15
TI  - Assessment of preferential T-helper 1 or T-helper 2 induction by low molecular 
      weight compounds using the local lymph node assay in conjunction with RT-PCR and 
      ELISA for interferon-gamma and interleukin-4.
PG  - 77-85
AB  - The local lymph node assay (LLNA) is a new and promising test in mice used to 
      identify contact allergens by means of dermal exposure. Experimentally this 
      assay, which comprises a sensitizing phase only, is also used to identify 
      respiratory allergens. Another, experimentally used test in mice to identify 
      allergens is also based on dermal exposure, but comprises both a sensitizing and 
      effector phase. In this latter test, it has been shown that contact allergens 
      preferentially induce a T-helper 1 (TH1) response, whereas respiratory allergens 
      preferentially induce a T-helper 2 (TH2) response. These responses can be 
      discriminated on the basis of cytokine production, such as IFN-gamma, which is 
      produced by TH1 cells, and IL-4, which is produced by TH2 cells. The aim of the 
      study was to establish whether the LLNA was sufficient to not only identify 
      allergens but also mark them as either a contact or a respiratory allergen. To 
      this end, LLNA responses to the contact allergen dinitrochlorobenzene (DNCB) and 
      the respiratory allergen trimellitic anhydride (TMA) were determined using 
      IFN-gamma and IL-4 mRNA expression and production as parameters. Topical 
      application of TMA resulted in a threefold higher lymphocyte proliferation 
      compared to DNCB 3 and 5 days after the first application, while a similar 
      proliferation was found from Day 7 and onward. RT-PCR showed a similar induction 
      of IFN-gamma and IL-4 mRNA expression. While both DNCB and TMA induced IFN-gamma 
      production, TMA but not DNCB induced IL-4 production. Thus, only IL-4 production 
      seemed a suitable parameter to discriminate between the two compounds. In a 
      second study, the respiratory allergens toluene-2,4-diisocyanate (TDI) and 
      phthalic anhydride (PA) were also assayed 7 days after the first application. 
      Topical application of DNCB and PA resulted in a similar lymphocyte 
      proliferation, while application of TMA and TDI resulted in a 1.8-fold higher 
      proliferation. IFN-gamma production was similar for DNCB, TMA, and TDI, and 
      fourfold lower for PA, while IL-4 production was similar for TMA, TDI, and PA, 
      and 24-fold lower for DNCB. In summary, both studies showed induction of IL-4 
      production by respiratory allergens, with little or no induction by the contact 
      allergen, holding promise for the possibility of identifying respiratory 
      allergens within the LLNA by measuring IL-4 production 7 days after the first 
      application.
CI  - Copyright 2000 Academic Press.
FAU - Vandebriel, R J
AU  - Vandebriel RJ
AD  - Laboratory for Pathology and Immunobiology, National Institute of Public Health 
      and the Environment, Bilthoven, 3720 BA, The Netherlands. r.vandebriel@rivm.nl
FAU - De Jong, W H
AU  - De Jong WH
FAU - Spiekstra, S W
AU  - Spiekstra SW
FAU - Van Dijk, M
AU  - Van Dijk M
FAU - Fluitman, A
AU  - Fluitman A
FAU - Garssen, J
AU  - Garssen J
FAU - Van Loveren, H
AU  - Van Loveren H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Allergens)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Phthalic Anhydrides)
RN  - 0 (RNA, Messenger)
RN  - 17X7AFZ1GH (Toluene 2,4-Diisocyanate)
RN  - 207137-56-2 (Interleukin-4)
RN  - 80T61EUU7H (trimellitic anhydride)
RN  - 82115-62-6 (Interferon-gamma)
RN  - UVL263I5BJ (phthalic anhydride)
SB  - IM
MH  - Allergens/*pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Dinitrochlorobenzene/immunology/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Interferon-gamma/*biosynthesis
MH  - Interleukin-4/*biosynthesis
MH  - Lymph Nodes/cytology/*drug effects/*immunology/metabolism
MH  - Lymphocyte Activation/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Weight
MH  - Phthalic Anhydrides/immunology/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Th1 Cells/drug effects/*immunology/metabolism
MH  - Th2 Cells/drug effects/*immunology/metabolism
MH  - Toluene 2,4-Diisocyanate/immunology/pharmacology
EDAT- 2000/01/19 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/01/19 09:00
PHST- 2000/01/19 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/01/19 09:00 [entrez]
AID - S0041-008X(99)98841-5 [pii]
AID - 10.1006/taap.1999.8841 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2000 Jan 15;162(2):77-85. doi: 10.1006/taap.1999.8841.