Objective: To explore whether mefloquine possesses the effect on granuloma formation induced by Schistosoma japonicum eggs.
Methods: Seventeen out of twenty-eight mice infected with 20 S. japonicum cercariae for 35 days were treated orally with mefloquine at a single dose of 200 mg/kg, and groups of 2-3 mice were sacrificed at various intervals post-treatment. The livers removed from each group of mice were fixed in 10% formaldehyde. While the remained 11 untreated mice divided into 6 groups (1-2 mice per group) were sacrificed at the same time periods as groups of mice treated with mefloquine, and their livers served as untreated corresponding controls. The granulomas with single egg in the center were counted and their diameters were measured using an ocular micrometer. The liver tissue sections were stained with hematoxylin and eosin (HE), Foot's or Mallory's methods for observation on histopathological alteration of egg granulomas, and on the appearance of reticular and collagen fibers within the granulomas.
Results: After infected mice were treated with mefloquine for 3, 7, 14, 21, 28 and 35 days, i.e., 38, 42, 49, 56, 63, and 70 days post-infection, the mean diameters of granuloma with single egg measured in the liver tissues section were (161 +/- 19), (175 +/- 13), (195 +/- 9), (171 +/- 40), (180 +/- 13), and (145 +/- 25) microm, respectively, and each of them was significantly lower than that of its corresponding control group of (189 +/- 18), (197 +/- 11), (211 +/- 12), (208 +/- 19), (203 +/- 16), and (207 +/- 36) microm (P < 0.01 or P < 0.05). Histopathological observation showed that in mice treated with mefloquine, the eosinophil-predominant inflammatory cells around the egg granuloma were sustained to 14-21 d post treatment (49-56 d post infection), which was significantly different from the corresponding control groups that all the eggs were surrounded by fibroblasts at 42 d post infection. Up to 28-35 d post treatment (63-70 d post infection), the boundary of egg granulomas distributed in the liver tissues of mefloquine treated groups was nearer in comparison to the corresponding control groups. Further observation on the reticular and collagen fibers within the egg granulomas by using specially staining methods demonstrated that in groups of mice treated with mefloquine for 2 weeks, the emergence and amount of the two kinds of fibers were delayed and less in comparison with corresponding control groups. After infected mice treated with mefloquine for 21 d (56 d post infection), the amount of the two kinds of fibers revealed in some egg granulomas was similar to the corresponding control group, but no further increase in the amount of the fibers, and seldom spread over the boundary of egg granuloma were seen 28 d and 35 d after treatment (63 d and 60 d post infection). While in corresponding control groups, the two kinds of fibers increased continuously with time post infection to become thick, and spread over the boundary of granuloma to further interconnect with the fibers stretched from the adjacent granuloma, and separate the liver tissue to form the grid-like structure.
Conclusion: Preliminary observation demonstrates that mefloquine possesses suppressive effect on granuloma formation induced by S. japonicum eggs.