Main Article Content
Leishmaniasis, adhesion molecules
Objectives-Methods. Visceral leishmaniasis (VL) is characterized by chronicity and relapses despite efficacious treatment. Acute and chronic inflammatory processes and concomitant disturbances in cell adhesion characterize the pathogenesis of the disease. To investigate these processes further we measured adhesion molecules (L-selectin, ICAM-1 and VCAM-1) serum levels in 16 children with VL, as well as in 20 healthy controls. All children were treated with liposomal amphotericin B (3 mg/kg) on days 1 to 5, 14, and 21. Measurements were performed at days 0, 15 and 30. Results. All children responded well to treatment in both clinical and laboratory terms. In three cases relapse occurred at 3, 5 and 6 months after treatment had ended. Serum L-selectin levels, both pre-treatment and post-treatment, did not significantly differ between patients and controls. VCAM-1 and ICAM-1 median levels were similar in patients and controls (P>0.05) at day 0 and significantly increased at day 15 (P<0.05). Interestingly, VCAM-1 and ICAM-1 dropped at day 30, with median levels comparable to those before treatment in the 13 children who subsequently had a good outcome without relapses (P>0.05), but not in the 3 patients who relapsed (P<0.05). Conclusions. Despite the small number of the patients, the changes in VCAM-1 and ICAM-1 levels indicate the anti-parasite activation of the immune system during the course of VL and the effect of treatment. Decline in post-treatment serum VCAM-1 and ICAM-1 levels might be used as a marker of treatment efficacy in childhood VL.
2. Rodrigues V, Cordeiro-da-Silva A, Laforge M, Silvestre R, Estaquier J. Regulation of immunity during visceral Leishmania infection. Parasit Vectors. 2016;9:118.
3. Figueira CP, Carvalhal DG, Almeida RA, Hermida M, Touchard D, Robert P, et al. Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin. Sci Rep. 2015;5:12862.
4. Golias C, Tsoutsi E, Matziridis A, Makridis P, Batistatou A, Charalabopoulos K. Review. Leukocyte and endothelial cell adhesion molecules in inflammation focusing on inflammatory heart disease. In Vivo. 2007;21(5):757-69.
5. Engwerda CR, Ato M, Stager S, Alexander CE, Stanley AC, Kaye PM. Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of Leishmania donovani infection. Am J Pathol. 2004;165(6):2123-33.
6. McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res. 2015;107(3):331-9.
7. Leon B, Ardavin C. Monocyte migration to inflamed skin and lymph nodes is differentially controlled by L-selectin and PSGL-1. Blood. 2008;111(6):3126-30.
8. Colpitts SL, Scott P. The early generation of a heterogeneous CD4+ T cell response to Leishmania major. J Immunol. 2010;185(4):2416-23.
9. Ready PD. Leishmaniasis emergence in Europe. Euro Surveill. 2010;15(10):19505.
10. Rahim KM, Ashkan MM. Epidemiological, clinical and therapeutic features of pediatric kala-azar. Southeast Asian J Trop Med Public Health. 2007;38(4):626-30.
11. Georgiadou SP, Stefos A, Spanakos G, Skrimpas S, Makaritsis K, Sipsas NV, et al. Current clinical, laboratory, and treatment outcome characteristics of visceral leishmaniasis: results from a seven-year retrospective study in Greece. Int J Infect Dis. 2015;34:46-50.
12. Kajaia M, Morse DL, Kamkamidze G, Butsashvili M, Chubabria G, Zenaishvili O, et al. Risk factors for relapse of visceral leishmaniasis in Georgia. Trop Med Int Health. 2011;16(2):186-92.
13. Kip AE, Balasegaram M, Beijnen JH, Schellens JH, de Vries PJ, Dorlo TP. Systematic review of biomarkers to monitor therapeutic response in leishmaniasis. Antimicrob Agents Chemother. 2015;59(1):1-14.
14. Vallur AC, Hailu A, Mondal D, Reinhart C, Wondimu H, Tutterrow Y, et al. Specific antibody responses as indicators of treatment efficacy for visceral leishmaniasis. Eur J Clin Microbiol Infect Dis. 2015;34(4):679-86.
15. Stanley AC, Dalton JE, Rossotti SH, MacDonald KP, Zhou Y, Rivera F, et al. VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental visceral leishmaniasis. PLoS Pathog. 2008;4(9):e1000158.
16. Olivier M, Gregory DJ, Forget G. Subversion mechanisms by which Leishmania parasites can escape the host immune response: a signaling point of view. Clin Microbiol Rev. 2005;18(2):293-305.
17. de Freitas EO, Leoratti FM, Freire-de-Lima CG, Morrot A, Feijo DF. The Contribution of Immune Evasive Mechanisms to Parasite Persistence in Visceral Leishmaniasis. Front Immunol. 2016;7:153.
18. Matte C, Casgrain PA, Seguin O, Moradin N, Hong WJ, Descoteaux A. Leishmania major Promastigotes Evade LC3-Associated Phagocytosis through the Action of GP63. PLoS Pathog. 2016;12(6):e1005690.
19. Mukherjee AK, Gupta G, Bhattacharjee S, Guha SK, Majumder S, Adhikari A, et al. Amphotericin B regulates the host immune response in visceral leishmaniasis: reciprocal regulation of protein kinase C isoforms. J Infect. 2010;61(2):173-84.
20. Kanegane H, Kasahara Y, Niida Y, Yachie A, Sughii S, Takatsu K, et al. Expression of L-selectin (CD62L) discriminates Th1- and Th2-like cytokine-producing memory CD4+ T cells. Immunology. 1996;87(2):186-90.
21. Miralles GD, Stoeckle MY, McDermott DF, Finkelman FD, Murray HW. Th1 and Th2 cell-associated cytokines in experimental visceral leishmaniasis. Infect Immun. 1994;62(3):1058-63.
22. Seixas Duarte MI, Tuon FF, Pagliari C, Kauffman MR, Brasil RA. Human visceral leishmaniasis expresses Th1 pattern in situ liver lesions. J Infect. 2008;57(4):332-7.