Lead (Pb) may affect humoral and cellular immunity, acting on lymphocytes as well as on granulocytes and monocytes. Cytokines and nitric oxide (NO) play a central role in the immune balance. In this study, plasma levels of nitrites and nitrates (NOx), IL2, IL4, IL6, IL10, TNF-α and INF-γ, were measured in healthy workers with very low (Pb-B =3.2 -18.0 μg/dL) and low (Pb-B = 9.1 -46.0 μg/dL) Pb-exposure compared to non-exposed workers. Low Pb-exposed workers (Pb-B =9.1 -46.0 μg/ dL) were found to have significantly higher plasma IL-10 levels, and tendentially higher plasma TNF-α levels compared to non-exposed workers. This is the first report of a significant increase of plasma IL-10 levels in Pb-exposed workers. Plasma IL-10 increase was influenced by blood Pb levels even after correction for main confounding factors. No difference was found in plasma NOx levels between Pb-exposed and non-exposed workers, which is in agreement with previous findings exclusively regarding groups in the general population. Low Pb-exposure can induce an increase of pro-inflammatory cytokines, such as TNF-α, with a consequent increase of other cytokines, such as IL-10, considered a T cell cross-regulatory factor, suggesting possible interference of Pb in the system of immunophlogosis. Human & Experimental Toxicology (2007) 26, 551 - 556

No abstract

We have studied the effect of lead on the fluidity of erythrocyte membrane to clarify if lead can interact in vivo with biological membranes. Erythrocyte membranes were chosen in our study because a decrease of red cell osmotic fragility is also evident in the absence of laboratory and clinical signs of anaemia. The study was undertaken using the Electron Spin Resonance technique with two spin labels 5-doxyl stearate and 16-doxyl-stearate, which probe the physical state of the polar surface and the inner core of the membrane respectively. Red blood cells and erythrocyte ghosts were prepared from the blood of workers occupationally exposed to lead and from healthy controls. The determinations of Pb blood, Pb urine, urine coproporphyrin and delta-aminolevulinic acid showed an increased internal dose of lead, but the ordinary metabolic and haematological parameters were in the normal range. Our results show that in lead workers there is a change in chemical physical state both in erythrocytes and erythrocyte ghosts consistent with a decrease of membrane fluidity, which is evident in the surface as well as in the inner core of the membrane. The degree of membrane fluidity modification does not appear correlated with blood lead level. Changes in the membrane structural organization could be the molecular basis of some pathological alterations induced by lead.

The effect of n-hexane metabolites on human polymorphonuclear leukocyte chemotaxis and luminol-dependent chemiluminescence was investigated. No effect was detected when 2-hexanol, 2-hexanone and gamma-valerolactone were used; 2,5-hexanedione at 75 micrograms/ml inhibited chemotaxis and a direct correlation between increasing the xenobiotic concentration and the degree of inhibition was found. Chemotactic peptide-induced chemiluminescence was not affected by 2,5-hexanedione. In order to clarify the phenomenon, plasma membrane fluidity was investigated by fluorescence polarization of the fluorescent probe trimethylammonium diphenylhexatriene. 2,5-hexanedione increased the membrane fluidity, while the other n-hexane metabolites did not change the degree of fluorescence polarization. Results suggest that the cellular functions modulated by membrane-cytoskeletal organization are affected by 2,5-hexanedione also at the low concentrations.

Continuous-filament glass fibers coated with organic agents, candidate asbestos substitutes, were assessed for their ability to elicit from normal human serum complement-derived cleavage products which are able to stimulate the chemotaxis and the respiratory burst of polymorphonuclear leukocytes. Glass fibers generated chemoattracting and respiratory stimulating factors for polymorphonuclears from human serum. The effect was dose related for chemotaxis from the serum fiber concentration of 75 micrograms/ml to 1,250 micrograms/ml. The serum chemoattracting activity, as well the respiratory stimulation, were dramatically impaired when serum had been preliminarily absorbed with antiC5 antiserum. Since the impairment of chemotactic activity occurred also in the presence of EDTA, but not in the presence of EGTA, we assumed an activation of the alternative complement pathway. Glass fibers were studied in comparison to a UICC sample of Canadian chrysotile asbestos, which is able to activate in vitro the alternative complement pathway. Glass fibers exhibited less ability than asbestos fibers to generate complement cleavage products with chemotactic activity for polymorphonuclears; however, they produced an activity about equal to 80% of a chemotactic standard stimulus such as zymosan-activated plasma.