Dexamethasone, a drug for attenuation of Schistosoma mansoni infection morbidity

Abstract

To investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic schistosomiasis, the study described in the present report evaluated the effects of dexamethasone on several parameters which reflect disease severity and morbidity. Parasitological, immunological, and histological parameters were analyzed in animals treated from the first day of infection or after 35 days of infection. In both situations, dexamethasone had no effect on the parasite burden but altered the egg distribution in tissue, indicating that under the schedule used it did not interfere with the development of adult worms or oviposition. Treated mice showed a decrease in the number of eggs in hepatic tissue, reduced granuloma sizes, reduced levels of granuloma maturation, and reduced collagen contents. Dexamethasone-treated mice also had decreased gamma interferon, interleukin-12 (IL-12), and IL-4 levels in serum and increased IL-10 levels in serum. Taken together, these data suggested a decrease in the severity of murine schistosomiasis and point to dexamethasone as a convenient and promising coadjuvant agent in the therapy of this infection.

FIG. 1.

Effect of dexamethasone on egg tissue distribution. Infected animals that were not treated (group I), treated with saline (group I + S), and treated with dexamethasone (groups I + Dex0 and I + Dex35) were killed at 120 days of infection. Tissues were digested as described by Cheever (11). The results represent the means ± standard deviations for eggs from the intestine or liver or for all eggs found in these tissues.

FIG. 2.

Dexamethasone reduces granuloma area. The sizes of granulomas from groups of infected animals that were not treated (groups I and I + S) and that were treated with dexamethasone (groups I + Dex0 and I + Dex35) on H-E-stained slides were evaluated as described in Materials and Methods. The area of granuloma from 20 to 25 granulomas per animal was determined by using at least five animals per group. A statistical difference between acutely infected and chronically infected animals is indicated by an asterisk, while the differences between nontreated animals (group I) and treated animals (groups I + Dex0 and I + Dex35) are indicated by P values. dpi, day postinfection.

FIG. 3.

Dexamethasone decreases the amount of collagen fiber deposition in hepatic granulomas. (a) Examples of images selectively expressing collagen in hepatic granulomas. (b) The area of collagen deposition was determined manually from 20 to 30 granulomas per animal, with at least five animals per group, by using images obtained by laser confocal microscopy from PSR-PMA-stained slides. A statistical difference between acute and chronic phase granulomas is represented by an asterisk (P < 0.012), while differences between the nontreated group (group I) and the dexamethasone-treated groups (groups I + Dex0 and I + Dex35) are expressed by P values. dpi, day postinfection.

FIG. 4.

Dexamethasone delays granuloma maturation. (a) Images representing the four stages of granuloma development (stages G1, G2, G3, and G4), as described in Materials and Methods (PMA-PSR staining). (b) An increase in the percentages of G1 stages and a decrease in the percentage of G4 stages were observed in dexamethasone-treated mice (groups I + Dex0 and I + Dex35). The results are expressed as means ± standard deviations. dpi, day postinfection.

FIG. 5.

Effects of dexamethasone on serum cytokine production. Cytokine levels in serum pooled from groups of nontreated and treated mice were measured by enzyme-linked immunosorbent assay as described in Materials and Methods. Asterisks represent statistical differences (P < 0.05) between the nontreated group (group I) and the dexamethasone-treated groups (groups I + Dex0 and I + Dex35). The results are expressed as means ± standard deviations.