TR,+N~.~+cTK,NS OF THE Rovnr SOCIETY OF TROPICAL. MEDICINE AND HYGIENE (1984) 78, 569-572 569 The immunological aspects of praziquantel in unsensitized mice with experimentally induced schistosome pulmonary granuloma SANAA S. BOTROS, AISHA A. METWALLY AND M. T. KHAYYAL Pharmacology Dept., Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba Guiza, P.B. 30, Egypt Summary The effects of praziquantel on cellular and humoral immune responses were studied in SwissAlbino mice and compared with the effects of potassium antimony tartrate. The experimental animals were antigenically primed by intravenous injection of Schistosoma mansoni eggs; the test drugs were given one day before egg injection and their effects monitored 16 days later. The size of the experimentally-induced pulmonary granulomata, immediate and delayed antigen-induced foot pad swelling, in vitro macrophage migration inhibition and the percentage of lymphocytes forming antibody and complement-depend&t rosetteswith erythiocytes (% EAC-R) were parametersused to assess the effect of the drugs. Praziquantel suppressed the size of pulmonary granulomata and the immediate and delayed foot pad reaction. Macrophage migration inhibition and the percentage of lymphocytes forming EAC-rosettes were not significantly affected. Tartar emetic was more effective as an immunosuppressant drug in these tests than praziquantel. Introduction Experimental work has shown that the granuloma- tous reaction of the host induced around tissue-bound Schistosoma mansoni eggs plays a major role in the pathogenesis of hepatosplenic schistosomiasis (WAR- REN, 1963; CHEEVER, 1965). In addition, WARREN et al. (1967) demonstrated that this inflammatory re- sponseto S. mansoni eggsis mostly an immunological reaction of the delayed hypersensitivity type. Interfer- ence in the course of infection with specific chemo- therapy may modulate this immune reaction and, accordingly, the pharmacologial assessmentof any schistosomicidal drug could appropriately include evaluation of its effects, if any,,on the host granuloma- tous response to S. mansom eggs. The present work investigates primarily the effect of the anti-schistosomal drug praziquantel (GONNERT & ANDREWS,1977) on the size of experimentally- induced pulmonary granulomata. Delayed foot pad swelling and macrophageinhibition were also studied as in vivo and in vitro correlates of the granulomatous hypersensitivity (BOROS et al., 1973; HANG et al., 1974) and effects of the drug on immediate foot pad swelling and on the percentage of lymphocytes forming EAC-rosettes were examined to detect any perturbations on the humoral arm of the immune system. Tartar emetic was used as a reference anti-schistosomal drug that also leads to immunosup- pression (MAHMOUD & WARREN, 1974). Materials and Methods Unsensitized mice 18 to 22 g in weight were divided into three groups: the first received prazic@antel suspended in 2% Cremouhor El given orallv in a dose of 3 x 250 mg/ker for three days; the-second received tartar emetic intraper; toneally in a dose of 5 x 20 mg/kg for five consecutive days; the third group served as untreated controls. Test drugs were given one day before intravenous injection of S. mansonieggs. The S. mans& eggs were obtained from the livers of mice eight weeks after infection with S. mansoni cercariae (COKER & LICHTENBERG, 1956) and each animal was given 1500eggsvia the dorsal tail vein. The effect of the solvent was tested in the same way. All the animals were killed 16 days after the injection of eggs and the lungs were sectioned and stained as described by WARREN et al. (1967) and BOROS & WARREN (1970). Lesions containing eggs in their centres were selected for measurement and the diameter of each pulmonary granulo- ma was obtained by measuring two diameters of the lesion at right angles to each other using an ocular micrometer. The mean diameter (u) of 100 lesions from the animals of each group ‘was obt&ed and the volume of each lesion was calculated from its mean diameter. Foot pad swelling was induced by the methods of BOROS Lk WARREN (1970). The test, done 24 hours before the animals were killed, was elicited by injection of 10 pg soluble egg antigen (SEA) protein. The mean difference in thickness between the antigen-injected and control saline-injected foot pads of each animal at one and 24 hours was taken as the net foot pad swelling (NFPS). Macrophage migration inhibition was assayed in a modification of the direct assay of FALK & ZABRISKIE (1971). SEA at a concentration of 2.5 pgiml was used to induce the reaction; macrophage migiation was assessed after 18 hours incuba- tion and quantitated by planimetry. Macrophage migration and inhibition was then calculated for each control and drug-treated animal as described by DAVID & DAVID (1971). Percentage of lymphocytes forming EAC-rosettes was estimated using the method of JONDAL et al. (1972) and LUCKASEN et al. (1974). The percentage reduction for any of the parameters used was calculated, and the significance of differences between controls and treated animals was evalu- ated by Student’s ‘t’ test. Results Effect of praziquantel and tartar emetic on the size of pulmonary granulomata Both drugs significantly reduced the diameter and volume of the granulomatous reaction around S. mansoni eggs (Table I). In Fig. 1 representative pulmonary granulomata in the lungs of drug-treated and control animals are illustrated. The areas of granulomata in treated animals were smaller than in untreated controls and tartar emetic produced a more marked reduction than praziquantel. Effect of praziquantel and tartar emetic on immediate and delayed foot pad swelling Praziquantel reduced both immediate and delayed reactions with similar efficacy (Table II). Tartar