Ss. Botros et al., Effect of combined praziquantel and recombinant glutathione S-transferase on resistance to reinfection in murine Schistosomiasis mansoni, INT J IMMUN, 22(11), 2000, pp. 979-988
This study was undertaken to evaluate the effect of recombinant Schistosoma
mansoni-26 Glutathione S-transferase (rSm 26 GST) or soluble egg antigen (
SEA) alone and in addition to praziquantel (PZQ) on the state of resistance
to S, mansoni reinfection. The associated changes in the immune responses
were evaluated. The experimental group of mice were injected intravenously
before S. mansoni infection (80 cercariae/mouse) either with rSm26 GST (1 m
ug x 4) or SEA (10 mug x 4) in addition to PZQ (2 x 500 mg/kg) administered
6 weeks post-infection. Seven control groups were used, three of them were
the infected (80 cercariae/mouse), the challenged (240 cercariae/mouse) an
d the infected challenged controls (80+240 cercariae/mouse). The rest of th
e four groups were the treated controls receiving: the GST-Lyzate, rSmGST,
SEA and PZQ in the same doses and at the same timings. Challenge infection
was conducted for all the groups 8 weeks post-infection. Animals were sacri
ficed 3 weeks post-challenge. After sacrifice animals were perfused and per
centage resistance to reinfection was calculated. Immune responses were ass
essed by the measurement of hepatic granuloma diameter, intralesional T-cel
l phenotypes and serum immunoglobulin isotypes. The highest percentage of r
esistance to reinfection was observed in rGST-treated group while the lowes
t percentage of resistance was detected in PZQ-treated group. Whereas in mi
ce receiving combined rGST or SEA and PZQ, percentage resistance to reinfec
tion was significantly higher than that in PZQ treated mice. The remarkable
reduction in granuloma diameter in rGST-treated group with or without PZQ
was associated with decrease in the intralesional L3T4+ and increase in Lyt
(2)(+) T-cell phenotypes. However, no special relationship was observed bet
ween the percentage of resistance and the changes in granuloma diameter or
intralesional T-cell phenotypes. The increase in percentage resistance to r
einfection was found accompanied by increased anti SWAP IgE. Combined rGST
and PZQ provided the complementary goals of improved state of resistance to
reinfection 'which was compromized after cure with PZQ' and the maximal re
duction in granuloma diameter. (C) 2000 Published by Elsevier Science Ltd o
n behalf of International Society for Immunopharmacology. All rights reserv
ed.