PMID- 14599759
OWN - NLM
STAT- MEDLINE
DCOM- 20031209
LR  - 20190819
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 193
IP  - 3
DP  - 2003 Dec 1
TI  - Identifying airway sensitizers: cytokine mRNA profiles induced by various 
      anhydrides.
PG  - 191-201
AB  - Exposure to low molecular weight (LMW) chemicals in the workplace has been linked 
      to a variety of respiratory effects. Within the LMW chemicals, one of the major 
      classes involved in these effects are the acid anhydrides. The immunological 
      basis of respiratory hypersensitivity involves CD4+ cells. By virtue of their 
      induction of cytokines typical of CD4+ T-helper type 2 (Th2) cells-interleukin 
      (IL)-4, 10, and 13-respiratory sensitizers may be identified and differentiated 
      from contact sensitizers which induce Th1 cytokines (IL-2 and IFN-gamma). Our 
      previous work suggested that the ribonuclease protection assay (RPA) was useful 
      in identifying the respiratory sensitizer, trimellitic anhydride (TMA), based on 
      quantitative differences in Th2 cytokine mRNA as compared to the contact 
      sensitizer dinitrochlorobenzene (DNCB). Therefore, the purpose of the studies 
      described in this report was to expand the chemicals tested in the RPA. To this 
      end, four acid anhydrides with known respiratory sensitization potential, TMA, 
      maleic anhydride (MA), phthalic anhydride (PA) and hexahydrophthalic anhydride 
      (HHPA), were tested. Although previously determined to induce immunologically 
      equivalent responses in a local lymph node assay (LLNA), the initial dose chosen 
      (2.5%) failed to induce Th2 cytokine mRNA expression. To determine if the lack of 
      cytokine expression was related to dose, LLNAs were conducted at higher doses for 
      each of the anhydrides. The highest doses evaluated (four- to six-fold higher 
      than those used in the initial RPA) gave equivalent proliferative responses for 
      the various anhydrides and were used for subsequent RPA testing. At these higher 
      doses, significant increases in Th2 versus Th1 cytokine mRNA were observed for 
      all anhydrides tested. These results suggest that the RPA has the potential to 
      serve as a screen for the detection of LMW airway sensitizing chemicals. However, 
      the basis for selecting immunologically equivalent doses may require some 
      modification.
FAU - Plitnick, L M
AU  - Plitnick LM
AD  - University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC 27599, 
      USA. lisa_plitnick@merck.com
FAU - Loveless, S E
AU  - Loveless SE
FAU - Ladics, G S
AU  - Ladics GS
FAU - Holsapple, M P
AU  - Holsapple MP
FAU - Smialowicz, R J
AU  - Smialowicz RJ
FAU - Woolhiser, M R
AU  - Woolhiser MR
FAU - Anderson, P K
AU  - Anderson PK
FAU - Smith, C
AU  - Smith C
FAU - Selgrade, M J K
AU  - Selgrade MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Anhydrides)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Anhydrides/*pharmacology
MH  - Animals
MH  - Cytokines/*drug effects/immunology/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Local Lymph Node Assay
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred CBA
MH  - RNA, Messenger/biosynthesis
MH  - Respiratory System/*drug effects
MH  - Th1 Cells/*drug effects/immunology/metabolism
MH  - Th2 Cells/*drug effects/immunology/metabolism
EDAT- 2003/11/06 05:00
MHDA- 2003/12/10 05:00
CRDT- 2003/11/06 05:00
PHST- 2003/11/06 05:00 [pubmed]
PHST- 2003/12/10 05:00 [medline]
PHST- 2003/11/06 05:00 [entrez]
AID - S0300483X03002646 [pii]
AID - 10.1016/s0300-483x(03)00264-6 [doi]
PST - ppublish
SO  - Toxicology. 2003 Dec 1;193(3):191-201. doi: 10.1016/s0300-483x(03)00264-6.