concanavalin-a and nickel-chloride

The aim of the present study was to investigate dose- and time-dependent effects of NiCl2 on T-lymphocyte and macrophage-derived cytokine production in rats. Moreover we have determined the concentrations of nickel in the plasma that are required to elicit alterations in T-lymphocyte and macrophage function. NiCl2 suppressed T-lymphocyte proliferation and Th1 (IFN-gamma) and Th2 (IL-10) cytokine production in a dose- and time-dependent fashion. In addition, NiCl2 inhibited production of the pro-inflammatory cytokine TNF-alpha and increased production of the anti-inflammatory cytokine IL-10 from lipopolysaccharide (LPS) stimulated cultures. We have determined that the minimal plasma concentrations of nickel required to provoke immunosuppression are in the range 209-585 ng/mL. In the time-course study NiCl2 (3.3 mg/kg) provoked immunological changes that were maximal 1 h following administration, and some of these changes persisted for up to 24 h post administration. Overall these data clearly demonstrate that NiCl2 suppresses T-cell function and promotes an immunosuppressive macrophage phenotype in rats. This study also indicates that measuring T-cell proliferation is as sensitive a marker of NiCl2-induced immunotoxicity as measuring T-cell or macrophage cytokine production. Co-measurement of circulating nickel concentrations and immune parameters yields valuable information with regard to the potency of nickel to alter immune function in vivo. These data also suggest that quite a large quantity of nickel needs to reach the systemic circulation before any adverse effects on immune function are observed.

Topics: Animals; Concanavalin A; Cytokines; Immunosuppressive Agents; In Vitro Techniques; Interferon-gamma; Interleukin-10; Leukocyte Count; Lymphocyte Activation; Macrophages; Male; Nickel; Rats; Rats, Sprague-Dawley; Th1 Cells; Th2 Cells

Effects of nickel and magnesium on the responsiveness of BALB/c mouse spleen lymphocytes to a mitogen, concanavalin A (Con A), were studied using the in vitro 3H-thymidine (TdR) incorporation test. Nickel chloride (NiCl2) and nickel subsulfide (Ni3S2) were found to suppress this response. The control level of TdR incorporation from a magnesium-free medium containing 0.625 microgram Con A/ml into trichloroacetic-acid-precipitable nucleoprotein was depressed by both nickel compounds in a dose-dependent manner to 3% of its original value by 0.25 mumol NiCl2/ml or 0.33 mumol Ni3S2/ml (5 micron particles). Magnesium stimulated TdR incorporation up to a maximum of 200% of the control level at concentrations greater than 2.0 mumol MgCl2/ml. Also, gradual increase of magnesium concentration in the culture medium up to 2.0 mumol/ml attenuated the effects of nickel, restoring the lymphocyte response to Con A to 43% of the control level at 0.25 mumol NiCl2/ml or to 30% at 0.33 mumol Ni3S2/ml. Higher concentrations of magnesium did not further enhance this responsiveness. These data suggest that the effect of magnesium upon early cellular response to nickel observed in vivo [Kasprzak et al.: Carcinogenesis 6: 1161-1166, 1985], which eventually results in a decreased tumor incidence, may be due in part to antagonism by magnesium of nickel suppression of the activity of T lymphocytes.

Topics: Animals; Concanavalin A; DNA; Drug Interactions; Female; Magnesium; Mice; Mice, Inbred BALB C; Nickel; Spleen; T-Lymphocytes