Granulocyte and plasma cytokine activity in acute cadmium intoxication in rats

Changes in the number and ex vivo function of peripheral blood neutrophils were investigated following intraperitoneal administration of cadmium-chlor ide in rats. Besides a dose-dependent increase in the number of peripheral blood neutrophils, changes were found in the functional state of isolated p olymorphonuclear leukocytes (PMNs). Increased spontaneous adhesion and acti vation, and TNF activity in a conditioned medium were observed in cultures of granulocytes in comparison to granulocytes from control (saline-treated) animals. Increased levels of plasma activity of inflammatory cytokines, tu mor necrosis factor (TNF) and interleukin-6 (IL-6) were noted following cad mium administration. Cytological signs of pulmonary inflammation were revea led histologically and the majority of neutrophils recovered from the lungs by enzyme digestion exhibited a capacity of nitroblue tetrazolium (NBT) re duction. Our data demonstrate that acute cadmium intoxication leads to a sy stemic inflammatory response characterized by numerical and functional chan ges in the granulocyte compartment and to increased levels of inflammation- related cytokine activity in the circulation. Correlations between the incr eased number of peripheral blood neutrophils and IL-6 plasma activity (r = 0.776, p < 0.00001) and the number of neutrophils recovered from the lung t issue (r = 0.893, p < 0.00001) suggested that systemic cadmium-induced infl ammation might be involved in the pulmonary toxicity of cadmium.