EPA Science Inventory

CYTOKINE MRNA PROFILES FOR ISOCYANATES WITH KNOWN AND UNKNOWN POTENTIAL TO INDUCE RESPIRATORY SENSITIZATION

Citation:

Plitnick, L. M., S. E. Loveless, G. S. Ladics, M. P. Holsapple, R J. Smialowicz, M. R. Woolshiser, P. K. Anderson, C. Smith, AND MJK Selgrade. CYTOKINE MRNA PROFILES FOR ISOCYANATES WITH KNOWN AND UNKNOWN POTENTIAL TO INDUCE RESPIRATORY SENSITIZATION. TOXICOLOGY. Elsevier Ireland Limited, Limerick, Ireland, 207:487-499, (2005).

Description:

Cytokine mRNA Profiles for Isocyanates with Known and Unknown Potential to Induce Respiratory Sensitization. Plitnick, L.M., Loveless, S.E., Ladics, G.S., Holsapple, M.P., Smialowicz, R.J., Woolhiser, M.R., Anderson, P.K., Smith, C., Sailstad, D.M. and Selgrade, M.J.K (2002) Toxicol. Appl. Pharmacol.

Abstract:
Isocyanates are members of the low molecular weight (LMW) chemical class and have been implicated in respiratory as well as contact hypersensitivity reactions. In order to protect workers who come in contact with such chemicals, an assay to identify respiratory sensitizers is needed. Current methodologies are based on the suggestion that respiratory sensitizers may be identified by their ability to induce a cytokine profile characteristic of a Th2 T cell response (IL4, IL10 and IL13). Previous studies from this laboratory have shown that mRNA levels for Th2 cytokines are elevated in response to acid anhydrides with known respiratory sensitizing potential and these elevations may be detected by ribonuclease protection assay (RPA). In the current study, 6 additional chemicals (toluene diisocyanate (TDI), diphenylmethane-4,4'-diisocyanate (MDI), dicyclohexylmethane-4,4'-diisocyanate (HMDI), isophorone diisocyanate (IPDI), p-tolyl (mono) isocyanate (TMI) and meta-tetramethylene xylene diisocyanate (TMXDI)) were evaluated for their ability to induce Th2 cytokine mRNA expression. RPA analysis showed that all 6 isocyanates tested induced the mRNA for cytokines characteristic of a Th2 response. Although the isocyanates tested appeared to differentiate into two groups, a high responding group and a low responding group, LLNAs confirmed that the doses chosen for the RPA were immunologically equivalent based on similar SI. In addition, 2 of the 3 low responders (TMI and TMXDI) induced levels of cytokine message statistically higher than DNCB, suggesting that all the isocyanates tested have the potential to induce respiratory hypersensitivity. Follow-up studies will be useful to determine whether these chemicals are actually sensitizers or if cytokine profiling is inappropriate for the identification of respiratory sensitizers.

Purpose/Objective:

to better identify respiratory sensitizers

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 02/07/2005
Completion Date: 02/07/2005
Record Last Revised: 10/15/2008
Record Created: 12/08/2004
Record Released: 12/08/2004
OMB Category: Other
Record ID: 105021

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

EXPERIMENTAL TOXICOLOGY DIVISION

IMMUNOTOXICOLOGY BRANCH