Abstract
Diethylcarbamazine (DEC) interferes with arachidonic acid metabolism for the clearance of microfilariae in Wuchereria bancrofti infected individuals. In this study, we have quantified the plasma concentrations of prostaglandin E2 (PGE2) and 6-keto-PGF1α, the end products of arachidonic acid metabolic pathway in microfilaraemics (DEC treated and untreated), and normal healthy individuals at pre- and 3,9,12,36, and 72 h of post-DEC treatment. We have also determined the microfilariae counts at pre and post day 2 (36 h) and day 3 (72 h) of DEC treatment by membrane filtration technique. Significant reduction in PGE2 and 6-keto-PGF1α concentrations was found at 12 h of DEC treatment. Rapid reduction in microfilarial counts was observed at 36 h of post-DEC treatment. Higher levels of prostaglandins were found at pre-treatment hours in microfilaraemics compared to normal healthy individuals (P < 0.05). Our findings indicate that DEC inhibits prostaglandins for the clearance of microfilariae, and increased levels of prostaglandins in microfilaraemics may be contributed by the parasite or host upon stimulation.
Similar content being viewed by others
References
Addiss DG, Eberhard ML, Lammie PJ, McNeeley MB, Lee SH, McNeeley DF, Spencer HC (1993) Comparative efficacy of clearing-dose and single high-dose ivermectin and diethylcarbamazine against Wuchereria bancrofti microfilaremia. Am J Trop Med Hyg 48:178–185
Brattig NW, Bazzocchi C, Kirschning CJ, Reiling N, Büttner DW, Ceciliani F, Geisinger F, Hochrein H, Ernst M, Wagner H, Bandi C, Hoerauf A (2004) The major surface protein of Wolbachia endosymbionts in filarial nematodes elicits immune responses through TLR2 and TLR4. J Immunol 173:437–445
Brattig NW, Schwohl A, Hoerauf A, Buttner DW (2009) Identification of the lipid mediator prostaglandin E2 in tissue immune cells of humans infected with the filarial Onchocerca volvulus. Acta Trop 112:231–235
Cesbron JY, Capron A, Vargaftig BB, Lagarde M, Pincemail J, Braquet P, Taelman H, Joseph M (1987) Platelets mediate the action of diethylcarbamazine on microfilariae. Nature 325:533–536
Chandrashekar R, Rao UR, Rajasekariah GR, Subrahmanyam D (1984) Isolation of microfilariae from blood on iso-osmotic percoll gradients. Indian J Med Res 79:497–501
Daugschies A, Joachim A (2000) Eicosanoids in parasites and parasitic infections. Adv Parasitol 46:181–240
Florencio MS, Peixoto CA (2003) The effects of diethylcarbamazine on the ultrastructure of microfilariae of Wuchereria bancrofti. Parasitology 126:551–554
Hawking F, Laurie W (1949) Action of hetrazan on filariasis and onchocerciasis. Lancet 2:146
Hawking F, Sewell P, Thurston JP (1950) The mode of action of hetrazan on filarial worms. Br J Pharmacol Chemother 5:217–238
Johnson P, Mackenzie CD, Denham DA, Suswillo RR (1988) The effect of diethylcarbamazine on the in vitro serum-mediated adherence of feline granulocytes to microfilariae of Brugia pahangi. Trop Med Parasitol 39:291–294
Kabututu Z, Martin SK, Nozaki T, Kawazu S, Okada T, Munday CJ, Duszenko M, Lazarus M, Thuita LW, Urade Y, Kubata BK (2003) Prostaglandin production from arachidonic acid and evidence for a 9,11-endoperoxide prostaglandin H2 reductase in Leishmania. Int J Parasitol 33:221–228
Kanesa-thasan N, Douglas JG, Kazura JW (1991) Diethylcarbamazine inhibits endothelial and microfilarial prostanoid metabolism in vitro. Mol Biochem Parasitol 49:11–19
Lammie PJ, Eberhard ML, Leiva LE, Lowrie RC Jr, Katz SP (1988) The effect of diethylcarbamazine treatment of bancroftian filariasis on the immunological reactivity of microfilaraemic individuals. Trans R Soc Trop Med Hyg 82:726–729
Liu LX, Weller PF (1990) Arachidonic acid metabolism in filarial parasites. Exp Parasitol 71:496–501
Liu LX, Weller PF (1992) Intravascular filarial parasites inhibit platelet aggregation. Role of parasite-derived prostanoids. J Clin Invest 89:1113–1120
Liu LX, Serhan CN, Weller PF (1990) Intravascular filarial parasites elaborate cyclooxygenase-derived eicosanoids. J Exp Med 172:993–996
Liu LX, Buhlmann JE, Weller PF (1992) Release of prostaglandin E2 by microfilariae of Wuchereria bancrofti and Brugia malayi. Am J Trop Med Hyg 46:520–523
Longworth DL, Foster DW, Dvorak AM, Weller PF (1985) Incorporation of arachidonic acid by microfilariae of Brugia malayi. J Infect Dis 152:1317–1323
Maizels RM, Denham DA (1992) Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug. Parasitology 105(Suppl):S49–S60
McCarthy JS, Guinea A, Weil GJ, Ottesen EA (1995) Clearance of circulating filarial antigen as a measure of the macrofilaricidal activity of diethylcarbamazine in Wuchereria bancrofti infection. J Infect Dis 172:521–526
McGarry HF, Plant LD, Taylor MJ (2005) Diethylcarbamazine activity against Brugia malayi microfilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway. Filaria J 4:4
Nelson FK, Greiner DL, Shultz LD, Rajan TV (1991) The immune-deficient scid mouse as a model for human lymphatic filariasis. J Exp Med 173:659–663
Noverr MC, Erb-Downward JR, Huffnagle GB (2003) Production of eicosanoids and other oxylipins by pathogenic eukaryotic microbes. Clin Microbiol Rev 16:517–533
Ottesen EA (1985) Efficacy of diethylcarbamazine in eradicating infection with lymphatic-dwelling filariae in humans. Rev Infect Dis 7:341–356
Ottesen EA (2000) The global program to eliminate lymphatic filariasis. Trop Med Int Health 5:591–594
Pani SP, Reddy GS, Das LK, Vanamail P, Hoti SL, Ramesh J, Das PK (2002) Tolerability and efficacy of single dose albendazole, diethylcarbamazine citrate (DEC) or coadministration of albendazole with DEC in the clearance of Wuchereria bancrofti in asymptomatic microfilaraemic volunteers in Pondicherry, South India: a hospital-based study. Filaria J 1:1
Pfarr KM, Debrah AY, Specht S, Hoerauf A (2009) Filariasis and lymphoedema. Parasite Immunol 31:664–672
Queto T, Xavier-Elsas P, Gardel MA, de Luca B, Barradas M, Masid D, E Silva PM, Peixoto CA, Vasconcelos ZM, Dias EP, Gaspar-Elsas MI (2010) Inducible nitric oxide synthase/CD95L-dependent suppression of pulmonary and bone marrow eosinophilia by diethylcarbamazine. Am J Respir Crit Care Med 181:429–437
Ramaswamy K, Kumar P, He YX (2000) A role for parasite-induced PGE2 in IL-10-mediated host immune regulation by skin stage schistosomula of Schistosoma mansoni. J Immunol 165:4567–4574
Simonsen PE, Magesa SM, Meyrowitsch DW, Malecela-Lazaro MN, Rwegoshora RT, Jaoko WG, Michael E (2005) The effect of eight half-yearly single-dose treatments with DEC on Wuchereria bancrofti circulating antigenaemia. Trans R Soc Trop Med Hyg 99:541–547
Sommer A, Rickert R, Fischer P, Steinhart H, Walter RD, Liebau E (2003) A dominant role for extracellular glutathione S-transferase from Onchocerca volvulus is the production of prostaglandin D2. Infect Immun 71:3603–3606
Tanioka T, Nakatani Y, Semmyo N, Murakami M, Kudo I (2000) Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem 275:32775–32782
Van Elssen CH, Vanderlocht J, Oth T, Senden-Gijsbers BL, Germeraad WT, Bos GM (2011) Inflammation-restraining effects of prostaglandin E2 on natural killer-dendritic cell (NK-DC) interaction are imprinted during DC maturation. Blood 118:2473–2482
Vickery AC, Nayar JK, Tamplin ML (1985) Diethylcarbamazine mediated clearance of Brugia pahangi microfilariae in immunodeficient nude mice. Am J Trop Med Hyg 34:476
WHO (1995) WHO model prescribing information: Drugs used in parasitic diseases. 2nd edn. 146
WHO (2010) Global program to eliminate lymphatic filariasis. Wkly Epidemiol Rec 85:365–372
Williams TJ, Morley J (1973) Prostaglandins as potentiators of increased vascular permeability in inflammation. Nature 246:215–217
Acknowledgment
Authors greatly acknowledge the technical support of Mrs. K. Vijalakshmi and S.M. Joseph for the collection of samples from the study subjects. Thanks are due to the entire team of clinical and epidemiology division for their cooperation during the entire period of study in recruiting the study subjects. Authors also acknowledge Dr. P. Vanamail for his statistical suggestions.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sankari, T., Hoti, S.L., Das, L.K. et al. Effect of Diethylcarbamazine (DEC) on prostaglandin levels in Wuchereria bancrofti infected microfilaraemics. Parasitol Res 112, 2353–2359 (2013). https://doi.org/10.1007/s00436-013-3399-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-013-3399-y