The Effect of Zinc Deficiency on Granuloma Formation, Liver Fibrosis, and Antibody Responses in Experimental Schistosomiasis

Abstract

The influence of various dietary zinc levels on the fibrotic aspects of granuloma formation and on the humoral response to schistosome egg antigens was investigated in C57Bl/6 mice by feeding groups of animals zinc-deficient diets. At six weeks of age, control and zinc-deficient mice were exposed individually to 50-60 cercariae of the Brazilian LE strain of Schistosoma mansoni. The animals were maintained on their respective diets for eight weeks postinfection, then all animals were killed and analyzed for body weight, spleen weight, collagen content of the liver, in vivo granulomatous histopathology, and antibody responses to soluble egg antigens. Zinc-deficient mice experienced stunted growth and reduced weight gain. Granulomatous hypersensitivity to schistosome eggs in the liver was measured in liver histopathologic sections using morphometric analysis and was found to be depressed in infected mice fed the moderately and the severely zinc-deficient diets. The low level of zinc in the diet also affected the humoral immune response of the host to schistosome egg antigens.

The use of a stereological method to estimate the volume of Schistosoma mansoni granulomas: the effect of zinc deficiency

“…Although there is no evidence to support this observation in the present investigation, the two studies are not directly comparable as mice were killed 8 weeks postinfection in one (Nawar et al, 1992) and 12 weeks post-infection in the other. Although the conventional, quantitative techniques are inherently biased, it is likely that the relatively small granulom as measured by Nawar et al (1992) reflect a true reduction in peak size of granulomas in zinc-deficient mice at 8 weeks post-infection, the result of impaired T-cell function. However, impaired T-cell function could also lead to impaired resolution of granulom as as well as impaired modulation of granulom atous hypersensitivity (Colley, 1975).…”

“…The median granuloma volume per egg (about 8.6 nl for both groups) is therefore likely to be an overestim ate, although the value lies within the range (0.9± 28 nl) reported by Cheever (1965). Nawar et al (1992), using conventional methods to estim ate granulom a size, observed that zinc-deficient mice had relatively small granulomas. Although there is no evidence to support this observation in the present investigation, the two studies are not directly comparable as mice were killed 8 weeks postinfection in one (Nawar et al, 1992) and 12 weeks post-infection in the other.…”

“…Nawar et al (1992), using conventional methods to estim ate granulom a size, observed that zinc-deficient mice had relatively small granulomas. Although there is no evidence to support this observation in the present investigation, the two studies are not directly comparable as mice were killed 8 weeks postinfection in one (Nawar et al, 1992) and 12 weeks post-infection in the other. Although the conventional, quantitative techniques are inherently biased, it is likely that the relatively small granulom as measured by Nawar et al (1992) reflect a true reduction in peak size of granulomas in zinc-deficient mice at 8 weeks post-infection, the result of impaired T-cell function.…”

“…Schistosoma mansoni infection in mice has proved useful as a model of hepatosplenic schistosomiasis in man, and, in studies on the effect of genetic, immunological, nutritional and other factors on morbidity in infected mice, granu-loma volume has been a widely used effect parameter (Von Lichtenberg, 1962;Cheever, 1965;Nawar et al, 1992). Conventional methods for the estimation of granulom a volumes have often used non-random sampling of sections, non-random sampling of visual ® elds, and the assumption that each granuloma is spherical.…”

The impact of zinc supplementation on Schistosoma mansoni reinfection rate and intensities: A randomized, controlled trial among rural Zimbabwean schoolchildren

“…Nonetheless, an increased stool volume is not a likely explanation of the difference in egg output since the weight gain was similar in the two groups over the 12 months study period (Friis et al, 1996). Effective formation of granulomata has been associated with facilitated excretion of the eggs (Doenhoff et al, 1986), and zinc deficiency has been shown to impair granuloma formation (Nawar et al, 1992). Hence, if this is the case in human infections, then it could have led to an underestimation of the true effect of zinc.…”