1921
Volume 100, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

We analyzed the association between insulin-like growth factor-I (IGF-I) and the pathogenesis of anemia during active visceral leishmaniasis (VL). Serum levels of IGF-I, IGF-binding protein 3 (IGFBP3), and cytokines were measured in samples from individuals with active VL and cured VL, asymptomatic -infected, and noninfected individuals. Then, we extended our analysis to VL dogs to evaluate hematimetric parameters, bone marrow alterations, and cytokine and IGF-I expression. We identified a positive correlation between lower IGF-I and IGFBP3 levels in active VL patients and lower hemoglobin levels. In infected dogs, there was a positive correlation between lower IGF-I expression in the bone marrow and lower peripheral blood hematocrit and hemoglobin levels. There was no correlation between decreased IGF-I level/expression and any measured cytokine serum levels in either host. The data suggest that low IGF-I expression is associated with pathogenesis of anemia in active VL, primarily in severe cases, by mechanisms other than alterations in cytokine production.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.17-0982
2019-02-11
2020-09-25
Loading full text...

Full text loading...

/deliver/fulltext/14761645/100/4/tpmd170982.html?itemId=/content/journals/10.4269/ajtmh.17-0982&mimeType=html&fmt=ahah

References

  1. Saporito L, Giammanco GM, De Grazia S, Colomba C, 2013. Visceral leishmaniasis: host-parasite interactions and clinical presentation in the immunocompetent and in the immunocompromised host. Int J Infect Dis 17: 572576.
    [Google Scholar]
  2. Carvalho MDT, Alonso DP, Vendrame CMV, Costa DL, Costa CHN, Werneck GL, Ribolla PEM, Goto H, 2014. Lipoprotein lipase and PPAR alpha gene polymorphisms, increased very-low-density lipoprotein levels, and decreased high-density lipoprotein levels as risk markers for the development of visceral leishmaniasis by Leishmania infantum. Mediators Inflamm 2014: 230129.
    [Google Scholar]
  3. Goto Y, Cheng J, Omachi S, Morimoto A, 2017. Prevalence, severity, and pathogeneses of anemia in visceral leishmaniasis. Parasitol Res 116: 457464.
    [Google Scholar]
  4. Costa CHN, Werneck GL, Costa DL, Holanda TA, Aguiar GB, Carvalho AS, Cavalcanti JC, Santos LS, 2010. Is severe visceral leishmaniasis a systemic inflammatory response syndrome? A case control study. Rev Soc Bras Med Trop. 43: 386392.
    [Google Scholar]
  5. Lafuse WP, Story R, Mahylis J, Gupta G, Varikuti S, Steinkamp H, Oghumu S, Satoskar AR, 2013. Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen. PLoS One 8: e59509.
    [Google Scholar]
  6. Cotterell SEJ, Engwerda CR, Kaye PM, 2000. Enhanced hematopoietic activity accompanies parasite expansion in the spleen and bone marrow of mice infected with Leishmania donovani. Infect Immun 68: 18401848.
    [Google Scholar]
  7. Pinto AI, Brown N, Preham O, Doehl JSP, Ashwin H, Kaye PM, 2017. TNF signalling drives expansion of bone marrow CD4+ T cells responsible for HSC exhaustion in experimental visceral leishmaniasis. PLoS Pathog 13: e1006465.
    [Google Scholar]
  8. Zumkeller W, 2002. The insulin-like growth factor system in hematopoietic cells. Leuk Lymphoma 43: 487491.
    [Google Scholar]
  9. O’Connor JC, McCusker RH, Strle K, Johnson RW, Dantzer R, Kelley KW, 2008. Regulation of IGF-I function by proinflammatory cytokines: at the interface of immunology and endocrinology. Cell Immunol 252: 91110.
    [Google Scholar]
  10. Santos-Oliveira JR, Regis EG, LealCá CRB, Cunha RV, BozzaPatrí PT, Da-Cruz AM, 2011. Evidence that lipopolisaccharide may contribute to the cytokine storm and cellular activation in patients with visceral leishmaniasis. PLoS Negl Trop Dis 5: e1198.
    [Google Scholar]
  11. dos Santos PL et al., 2016. The severity of visceral leishmaniasis correlates with elevated levels of serum IL-6, IL-27 and sCD14. PLoS Negl Trop Dis 10: e0004375.
    [Google Scholar]
  12. Arkins S, Rebeiz N, Brunke-Reese DL, Biragyn A, Kelley KW, 1995. Interferon-gamma inhibits macrophage insulin-like growth factor-I synthesis at the transcriptional level. Mol Endocrinol 9: 350360.
    [Google Scholar]
  13. Fan J, Char D, 1995. Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by tumor necrosis factor. Am J Physiol 269: R1204R1212.
    [Google Scholar]
  14. Askenasy N, 2015. Interferon and tumor necrosis factor as humoral mechanisms coupling hematopoietic activity to inflammation and injury. Blood Rev 29: 1115.
    [Google Scholar]
  15. Braz RFS, Nascimento ET, Martins DRA, Wilson ME, Pearson RD, Reed SG, Jeronimo SMB, 2002. The sensitivity and specificity of Leishmania chagasi recombinant K39 antigen in the diagnosis of American visceral leishmaniasis and in differentiating active from subclinical infection. Am J Trop Med Hyg 67: 344348.
    [Google Scholar]
  16. Hasegawa MY, Kohayagawa A, Brandão LP, Morgulis MSFa, Hagiwara MK, 2005. Evaluation of neutrophil oxidative metabolism in canine monocytic ehrlichiosis. Vet Clin Pathol 34: 213217.
    [Google Scholar]
  17. Messick J, 2010. Erithrocytes. Schalm’s Veterinary Hematology. Ames, IA: Wiley-Blackwell.
    [Google Scholar]
  18. Harvey JW, Stevens A, Lowe JS, Scott I, 2012. Veterinary Hematology. St. Louis, MO: Elsevier Inc.
    [Google Scholar]
  19. Livak KJ, Schmittgen TD, 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods 25: 402408.
    [Google Scholar]
  20. Elmlinger MW, Kühnel W, Weber MM, Ranke MB, 2004. Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3). Clin Chem Lab Med 42: 654664.
    [Google Scholar]
  21. Lopes AC, 2006. Tratado de Clínica médica, Vol. 3. São Paulo, Roca.
    [Google Scholar]
  22. Daneshbod Y, Dehghani SJ, Daneshbod K, 2010. Bone marrow aspiration findings in kala-azar. Acta Cytol 54: 1224.
    [Google Scholar]
  23. Loría-Cervera EN, Andrade-Narváez FJ, 2014. Animal models for the study of leishmaniasis immunology. Rev Inst Med Trop Sao Paulo 56: 111.
    [Google Scholar]
  24. Nicolato RDC et al., 2013. Clinical forms of canine visceral leishmaniasis in naturally Leishmania infantum-infected dogs and related myelogram and hemogram changes. PLoS One 8: e82947.
    [Google Scholar]
  25. Varma N, Naseem S, 2010. Hematologic changes in visceral leishmaniasis/kala azar. Indian J Hematol Blood Transfus 26: 7882.
    [Google Scholar]
  26. Welniak LA, Karas M, Yakar S, Anver MR, Murphy WJ, LeRoith D, 2004. Effects of organ-specific loss of insulin-like growth factor-I production on murine hematopoiesis. Biol Blood Marrow Transplant 10: 3239.
    [Google Scholar]
  27. Savino W, Smaniotto S, Dardenne M, 2005. Hematopoiesis. Varela-Nieto I, Chowen JA, eds. The Growth Hormone/Insulin-Like Growth Factor Axis During Development. Advances in Experimental Medicine and Biology, Vol. 567. Boston, MA: Springer.
    [Google Scholar]
  28. Succurro E, Arturi F, Caruso V, Rudi S, Sciacqua A, Andreozzi F, Hribal ML, Perticone F, Sesti G, 2011. Low insulin-like growth factor-1 levels are associated with anaemia in adult non-diabetic subjects. Thromb Haemost 105: 365370.
    [Google Scholar]
  29. Ratajczak J, Zhang Q, Pertusini E, Wojczyk BS, Wasik MA, Ratajczak MZ, 1998. The role of insulin (INS) and insulin-like growth factor-I (IGF-I) in regulating human erythropoiesis. Studies in vitro under serum-free conditions—comparison to other cytokines and growth factors. Leukemia 12: 371381.
    [Google Scholar]
  30. Miniero R, Altomare F, Rubino M, Matarazzo P, Montanari C, Petri A, Raiola G, Bona G, 2012. Effect of recombinant human growth hormone (rhGH) on hemoglobin concentration in children with idiopathic growth hormone deficiency-related anemia. J Pediatr Hematol Oncol 34: 407411.
    [Google Scholar]
  31. Choi JW, Kim SK, 2004. Association of serum insulin-like growth factor-I and erythropoiesis in relation to body iron status. Ann Clin Lab Sci 34: 324328.
    [Google Scholar]
  32. Miljuš G, Malenković V, Nedić O, 2013. The importance of metal ions for the formation and isolation of insulin-like growth factor-binding protein 3–transferrin (IGFBP-3–Tf) complexes, and the analysis of their physiological involvement. Metallomics 5: 251.
    [Google Scholar]
  33. Pinho FA, Magalhães NA, Silva KR, Carvalho AA, Oliveira FLL, Ramos-Sanchez EM, Goto H, Costa FAL, 2013. Divergence between hepatic insulin-like growth factor (IGF)-I mRNA expression and IGF-I serum levels in Leishmania (Leishmania) infantum chagasi-infected dogs. Vet Immunol Immunopathol 151: 163167.
    [Google Scholar]
  34. Lemaire J, Mkannez G, Guerfali FZ, Gustin C, Attia H, Sghaier RM, Dellagi K, Laouini D, Renard P, Sysco-Consortium, 2013. MicroRNA expression profile in human macrophages in response to leishmania major infection. PLoS Negl Trop Dis 7: e2478.
    [Google Scholar]
  35. Marini MA, Mannino GC, Fiorentino TV, Andreozzi F, Perticone F, Sesti G, 2017. A polymorphism at IGF1 locus is associated with anemia. Oncotarget 8: 3239832406.
    [Google Scholar]
  36. Koury MJ, 2014. Abnormal erythropoiesis and the pathophysiology of chronic anemia. Blood Rev 28: 4966.
    [Google Scholar]
  37. Preham O, Pinho FA, Pinto AI, Rani GF, Brown N, Hitchcock IS, Goto H, Kaye PM, 2018. CD4+ T cells alter the stromal microenvironment and repress medullary erythropoiesis in murine visceral leishmaniasis. Front Immunol 9: 112.
    [Google Scholar]
  38. De Bruin AM, Voermans C, Nolte MA, 2014. Impact of interferon-γ on hematopoiesis. Blood 124: 24792486.
    [Google Scholar]
  39. Choi I, Muta K, Wickrema A, Krantz SB, Nishimura J, Nawata H, 2000. Interferon gamma delays apoptosis of mature erythroid progenitor cells in the absence of erythropoietin. Blood 95: 37423749.
    [Google Scholar]
  40. Grigorakaki C, Morceau F, Chateauvieux S, Dicato M, Diederich M, 2011. Tumor necrosis factor alpha-mediated inhibition of erythropoiesis involves GATA-1/GATA-2 balance impairment and PU.1 over-expression. Biochem Pharmacol 82: 156166.
    [Google Scholar]
  41. Schubert T, Echtenacher B, Hofstädter F, Männel DN, 2003. TNF-independent development of transient anemia of chronic disease in a mouse model of protracted septic peritonitis. Lab Invest 83: 17431750.
    [Google Scholar]
  42. Schubert TE, Echtenacher B, Hofstädter F, Männel DN, 2005. Failure of interferon-gamma and tumor necrosis factor in mediating anemia of chronic disease in a mouse model of protracted septic peritonitis. Int J Mol Med 16: 753758.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.17-0982
Loading
/content/journals/10.4269/ajtmh.17-0982
Loading

Data & Media loading...

Supplemental table

  • Received : 15 Dec 2017
  • Accepted : 04 Jan 2019
  • Published online : 11 Feb 2019
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error