Changed distribution and immune effects of nickel augment viral-induced inflammatory heart lesions in mice

Abstract

We have used the myocarditic coxsackievirus B3 (CB3) infection in Balb/c mice to investigate immunotoxic effects of a ten-week low-dose (0.002 M) administration of nickel chloride (NiCl 2) prior to infection. This dose did not influence CB3-induced mortality. Whole-body autoradiography of [ 63Ni] during the disease showed the pancreas, lungs and myocardium to be new target organs in this disease. Seven days after the inoculation, impulse counting of these organs showed the infection-induced increase of [ 63Ni] to be 5-fold ( P < 0.01) in the pancreas, 2.2-fold ( P < 0.05) in the lungs and 1.3-fold ( P < 0.05) in the heart. Nickel tended to increase spleen B- and T-cell activities, but thymocyte activity was unaffected. The activity of spleen natural killer (NK) cells decreased by 30% ( P < 0.05), whereas blood-cell activity in fact increased by 51% ( P < 0.05). The inflammatory and necrotic lesions in the ventricular myocardium seven days after the inoculation covered 3.31% of the tissue section area in infected control mice. This damage was increased by 43% (to 4.74% of the tissue section area) in nickel-treated mice. The response pattern of lymphocyte subsets in situ in myocardial inflammatory lesions was elucidated by an immune histochemical staining technique. The number of cytotoxic T-cells, helper T-cells and Mac 2 + cells (macrophages) in these lesions decreased by 46% ( P < 0.05), 41% ( P < 0.05) and 27% (not significant), respectively, with the nickel treatment. The number of helper T-cells was negatively correlated to the size of the inflammatory area ( r = −0.529, P < 0.02). The results indicate that nickel may contribute to the progression of target organ pathology in infection-induced diseases of an autoimmune and/or inflammatory character, such as diabetes and myocarditis.