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Immunotoxicity of organophosphorus compounds. Modulation of cell-mediated immune responses by inhibition of monocyte

A H Esa1, G A Warr, D S Newcombe

  • 1Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.

Clinical Immunology and Immunopathology
|October 1, 1988
PubMed

Insights

Certain organophosphorus compounds (OP) suppress human immune responses by impairing monocyte function. These chemicals, used as flame retardants and plasticizers, inhibit antigen presentation and lymphocyte proliferation at low concentrations.

Area of Science:

  • Immunology
  • Toxicology
  • Environmental Health

Background:

  • Organophosphorus compounds (OP) are widely used as flame retardants and plasticizers.
  • Potential immunotoxic effects of these widely dispersed chemicals require thorough investigation.
  • Human cell-mediated immune responses are crucial for defense against pathogens and disease.

Purpose of the Study:

  • To evaluate the effects of commercially relevant organophosphorus compounds on human in vitro cell-mediated immune responses.
  • To identify specific immune cell types and functions targeted by these compounds.
  • To determine the concentrations at which these effects occur.

Main Methods:

  • In vitro assays using human peripheral blood mononuclear cells (PBMCs).
  • Assessment of antigen-specific lymphocyte proliferation and mitogenesis.
  • Monocyte-lymphocyte co-culture experiments to delineate cellular targets.
  • Direct assessment of monocyte antigen presentation inhibition.

Main Results:

  • Triphenylphosphine oxide (TPPO) and tetra-o-cresylpiperazinyl diphosphoamidate (TCPD) significantly suppressed antigen-specific lymphocyte proliferation at nontoxic concentrations (0.1-20 microM).
  • Mitogenesis was less sensitive, affected only by TCPD.
  • Evidence suggests OP compounds interfere with monocyte function rather than directly acting on lymphocytes.
  • Triphenyl phosphate (TPP), triphenyl thiophosphate (TPTP), TPPO, and TCPD significantly inhibited monocyte antigen presentation at concentrations as low as 1 microM.

Conclusions:

  • Several organophosphorus compounds exhibit immunomodulatory effects on human immune cells in vitro.
  • These compounds primarily target monocyte functions, including antigen presentation, leading to suppressed lymphocyte responses.
  • The findings highlight potential risks associated with environmental exposure to these chemicals, impacting cell-mediated immunity.

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