Pro and Anti-inflammatory Cytokine Production in CD4+ T Lymphocytes in Children with Asthma and Allergic Rhinitis Exposed to the Monocyte Locomotion Inhibitory Factor (MLIF)
Entamoeba histolytica produces, in axenic culture, the monocytes locomotion inhibitory factor (MLIF), a oligopeptide with selective anti-inflammatory properties. We evaluated the effect of MLIF on the expression of pro- and anti-inflammatory cytokines in CD4+ T lymphocytes from children with asthma and allergic rhinitis. Twelve children with severe asthma, 12 children with allergic rhinitis and 6 healthy controls were recruited for this study between May and December 2016. CD4+ T cells were cultured for 24 h at 37°C, 5% CO2 in the presence of MLIF, 1-phorbol 12-myristate 13-acetate (PMA), MLIF+PMA or RPMI. Interleukin-10 (IL-10), IL-4, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) expression levels were measured in the supernatants of T-cell cultures using the enzyme-linked immunosorbent assay (ELISA). Pro- and anti-inflammatory cytokines were inhibited by MLIF (IFN-γ p=0.0036, TNF-α p<0.001, IL-4 p=0.0082) in asthmatic patients, however IFN-γ was not significantly inhibited (NS) in patients with allergic rhinitis when compared to the RPMI group. In CD4+ T cells treated with PMA+MLIF, the expression levels of IFN-γ, TNF-α and IL-4 were strongly inhibited (p<0.001, p<0.001 and p<0.0094), compared to PMA treatment alone, for both, rhinitis and asthma. IL-10 expression was not affected by MLIF in neither of the two diseases. We conclude that MLIF alters the pro/anti-inflammatory balance and induces inhibition of IL-4, IFN-γ and TNF-α, but does not affect IL-10.
2. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008; (Suppl 86):8-160.
3. Aryan Z, Compalati E, Canonica GW, Rezaei N. Allergen-specific immunotherapy in asthmatic children: from the basis to clinical applications. Expert Rev Vaccines 2013; 12(6):639-59.
4. Bousquet PJ, Combescure C, Klossek JM, Daurès JP, Bousquet J. Change in visual analog scale score in a pragmatic randomized cluster trial of allergic rhinitis. J Allergy Clin Immunol 2009; 123(6):1349-54.
5. Hawrylowicz CM, O'Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol 2005; 5(4):271-83.
6. Parronchi P, Macchia D, Piccinni MP, Biswas P, Simonelli C, Maggi E, et al. Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. Proc Natl Acad Sci USA 1991; 88(10):4538-42.
7. Kretschmer R, Collado ML, Pacheco MG, Salinas MC, López-Osuna M, Lecuona M, et al. Inhibition of human monocyte locomotion by products of axenically grown E. histolytica. Parasite Immunol 1985; 7(5):527-43.
8. Rojas-Dotor S, Rico G, Pérez J, Velázquez J, Silva R, Morales E, et al. Cytokine expression in CD4(+) cells exposed to the monocyte locomotion inhibitory factor produced by Entamoeba histolytica. Parasitol Res 2006; 98(5):493-5. 9. Rojas-Dotor S, Segura-Méndez NH, Miyagui-Namikawa K, Mondragón-González R. Expression of resistin, CXCR3, IP-10, CCR5 and MIP-1α in obese patients with different severity of asthma. Biol Res 2013; 46(1):13-20.
10. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, Fitzgerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008; 31(1):143-78.
11. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 1968; 97:77-89.
12. Giménez-Scherer JA, Arenas E, Díaz L, Rico G, Fernández J, Kretschmer R. Effect of the monocyte locomotion inhibitory factor (MLIF) produced by Entamoeba histolytica on the expression of cell adhesion molecules (CAMs) in the skin of guinea pigs. Arch Med Res 2000; 31(4 Suppl):S92-3.
13. Giménez-Scherer JA, Pacheco-Cano MG, Cruz de Lavín E, Hernández-Jáuregui P, Merchant MT, Kretschmer RR. Ultrastructural changes associated with the inhibition of monocyte chemotaxis caused by products of axenically grown Entamoeba histolytica. Lab Invest 1987; 57(1):45-51.
14. Kretschmer RR, Rico G, Giménez JA. A novel anti-inflammatory oligopeptide produced Entamoeba histolytica. Mol Biochem Parasitol 2001; 112(2):201-9.
15. Seder RA, Paul WE. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol 1994; 12:635-73.
16. Selzman CH, McIntyre RC Jr, Shames BD, Whitehill TA, Banerjee A, Harken AH. Interleukin-10 inhibits human vascular smooth muscle proliferation. J Mol Cell Cardiol 1998; 30(4):889-96.
17. Kretschmer RR, Castro EM, Pacheco G, Rico G, Díaz-Guerra O, Arellano J. The role of mannose in the receptor of the monocyte locomotion inhibitory factor produced by Entamoeba histolytica. Parasitol Res 1991; 77(5):374-8.
18. Rico G, Díaz-Guerra O, Kretschmer RR. Cyclic nucleotide changes induced in human leukocytes by a product of axenically grown Entamoeba histolytica that inhibits human monocyte locomotion. Parasitol Res 1995; 81(2):158-62.