Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl 2 treatment decreases T helper cell type 1‐like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice

Summary 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 .