Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice

Clin Exp Immunol. 2007 Oct;150(1):189-97. doi: 10.1111/j.1365-2249.2007.03474.x. Epub 2007 Aug 2.

Abstract

Lyme borreliosis is a complex infection, where some individuals develop so-called 'chronic borreliosis'. The pathogenetic mechanisms are unknown, but the type of immune response is probably important for healing. A strong T helper cell type 1 (Th1)-like response has been suggested as crucial for eradication of Borrelia and for avoiding development of chronic disease. Many studies aimed at altering the Th1/Th2 balance in Lyme arthritis employed mice deficient in cytokine genes, but the outcome has not been clear-cut, due possibly to the high redundancy of cytokines. This study aimed at studying the importance of the Th1/Th2 balance in murine Borrelia arthritis by using the Th2-deviating effect of subtoxic doses of inorganic mercury. Ninety-eight C3H/HeN mice were divided into four groups: Borrelia-infected (Bb), Borrelia-infected exposed to HgCl(2) (BbHg), controls exposed to HgCl(2) alone and normal controls. Mice were killed on days 3, 16, 44 and 65 post-Borrelia inoculation. Arthritis severity was evaluated by histology, spirochaetal load determined by Borrelia culture, IgG2a- and IgE-levels analysed by enzyme-linked immunosorbemt assay (ELISA) and cytokine-secreting cells detected by enzyme-linked immunospot (ELISPOT). BbHg mice showed less severe histological arthritis, but delayed eradication of spirochaetes compared to Bb mice, associated with increased levels of IgE (Th2-induced) and decreased levels of IgG2a (Th1-induced), consistent with a Th2-deviation. Both the numbers of Th1 and Th2 cytokine-secreting cells were reduced in BbHg mice, possibly explained by the fact that numbers of cytokine-secreting cells do not correlate with cytokine concentration. In conclusion, this study supports the hypothesis that a Th1-like response is required for optimal eradication of Borrelia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Infectious / drug therapy*
  • Arthritis, Infectious / immunology
  • Arthritis, Infectious / microbiology
  • Arthritis, Infectious / pathology
  • Body Weight / drug effects
  • Borrelia burgdorferi / isolation & purification
  • Disease Models, Animal
  • Female
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Joints / pathology
  • Lyme Disease / drug therapy*
  • Lyme Disease / immunology*
  • Lyme Disease / microbiology
  • Lyme Disease / pathology
  • Lymph Nodes / immunology
  • Mercuric Chloride / therapeutic use*
  • Mice
  • Mice, Inbred C3H
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology

Substances

  • Immunoglobulin G
  • Interleukin-12
  • Interleukin-4
  • Immunoglobulin E
  • Mercuric Chloride
  • Interferon-gamma