Association between Insulin-Like Growth Factor-I Levels and the Disease Progression and Anemia in Visceral Leishmaniasis

Pinho, Flaviane Alves de; Vendrame, Célia Maria Vieira; Maciel, Bruna Leal Lima; Silva, Lucilene dos Santos; Miyashiro, Samantha Ive; Jerônimo, Selma M. B.; Goto, Hiro

doi:10.4269/ajtmh.17-0982

Cited by 3 publications

(4 citation statements)

References 38 publications

(43 reference statements)

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“…The evident dichotomy between GR and GNR dogs allowed for identifying two laboratory parameters predictive of therapeutic success: erythrocyte counts and serum phosphorus dosage. Anemia is commonly observed in human and canine leishmaniasis and can originate from reduced production and/or increased destruction of erythrocytes [27,40,41]. During chronic inflammatory diseases, anemia results from low iron circulating levels, while inflammatory cytokines such TFN-α, IL-1 and IFN-γ inhibit erythropoiesis, and erythrocyte membrane damage by oxidizing agents shortens the lifespan of erythrocytes [42].…”

Section: Discussionmentioning

confidence: 99%

Mathematical Modelling Using Predictive Biomarkers for the Outcome of Canine Leishmaniasis upon Chemotherapy

et al. 2020

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Prediction parameters of possible outcomes of canine leishmaniasis (CanL) therapy might help with therapeutic decisions and animal health care. Here, we aimed to develop a diagnostic method with predictive value by analyzing two groups of dogs with CanL, those that exhibited a decrease in parasite load upon antiparasitic treatment (group: responders) and those that maintained high parasite load despite the treatment (group: non-responders). The parameters analyzed were parasitic load determined by q-PCR, hemogram, serum biochemistry and immune system-related gene expression signature. A mathematical model was applied to the analysis of these parameters to predict how efficient their response to therapy would be. Responder dogs restored hematological and biochemical parameters to the reference values and exhibited a Th1 cell activation profile with a linear tendency to reach mild clinical alteration stages. Differently, non-responders developed a mixed Th1/Th2 response and exhibited markers of liver and kidney injury. Erythrocyte counts and serum phosphorus were identified as predictive markers of therapeutic response at an early period of assessment of CanL. The results presented in this study are highly encouraging and may represent a new paradigm for future assistance to clinicians to interfere precociously in the therapeutic approach, with a more precise definition in the patient’s prognosis.

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Section: Discussionmentioning

confidence: 99%

Mathematical Modelling Using Predictive Biomarkers for the Outcome of Canine Leishmaniasis upon Chemotherapy

et al. 2020

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“…When we evaluated both IGF-I and IGF-binding protein-3 (IGFBP3) serum levels in samples collected from active VL patients, we observed low levels of both IGF-I and IGFBP3 [ 109 ]. Based on these unexpected data, mainly in VL, where we observe massive parasite proliferation in inner organs and considering experimental data showing no evident IGF-I effect on parasite growth, we should consider the participation of IGF-I in another way in the biology of Leishmania .…”

Section: Igf-i In Human Leishmaniasismentioning

confidence: 99%

“…Based on these unexpected data, mainly in VL, where we observe massive parasite proliferation in inner organs and considering experimental data showing no evident IGF-I effect on parasite growth, we should consider the participation of IGF-I in another way in the biology of Leishmania . Further IGF-I low levels in active VL were also seen in canine VL [ 109 , 110 ] and human VL patients [ 111 ]. We do not have any element to envisage whether an IGF-I low level seen in active VL cases influences nonspecific processes related to parasite growth or adaptive immune response.…”

Section: Igf-i In Human Leishmaniasismentioning

confidence: 99%

“…Thus, we suggested that IGF-I has a pathogenic role in VL anemia without any correlation with cytokine levels. IFN- γ was shown negatively correlated with anemia; thus, we suggested that both IFN- γ and IGF-I contribute to the pathogenesis of anemia in active VL but independently [ 109 ]. The experimental data in murine VL showing CD4 + T cells producing IFN- γ with alteration in the stromal microenvironment in bone marrow linked to anemia development reinforced the importance of IFN- γ in the pathogenesis of anemia in active VL [ 115 ].…”

Section: Igf-i In Human Leishmaniasismentioning

confidence: 99%

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Pleiotropic Effect of Hormone Insulin-Like Growth Factor-I in Immune Response and Pathogenesis in Leishmaniases

Reis

Ramos-Sanchez

Araújo

et al. 2021

Journal of Immunology Research

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Leishmaniases are diseases caused by several Leishmania species, and many factors contribute to the development of the infection. Because the adaptive immune response does not fully explain the outcome of Leishmania infection and considering that the initial events are crucial in the establishment of the infection, we investigated one of the growth factors, the insulin-like growth factor-I (IGF-I), found in circulation and produced by different cells including macrophages and present in the skin where the parasite is inoculated. Here, we review the role of IGF-I in leishmaniasis experimental models and human patients. IGF-I induces the growth of different Leishmania species in vitro and alters the disease outcome increasing the parasite load and lesion size, especially in L. major- and L. amazonensis-infected mouse leishmaniasis. IGF-I affects the parasite interacting with the IGF-I receptor present on Leishmania. During Leishmania-macrophage interaction, IGF-I acts on the arginine metabolic pathway, resulting in polyamine production both in macrophages and Leishmania. IGF-I and cytokines interact with reciprocal influences on their expression. IL-4 is a hallmark of susceptibility to L. major in murine leishmaniasis, but we observed that IGF-I operates astoundingly as an effector element of the IL-4. Approaching human leishmaniasis, patients with mucosal, disseminated, and visceral diseases presented surprisingly low IGF-I serum levels, suggesting diverse effects than parasite growth. We observed that low IGF-I levels might contribute to the inflammatory response persistence and delayed lesion healing in human cutaneous leishmaniasis and the anemia development in visceral leishmaniasis. We must highlight the complexity of infection revealed depending on the Leishmania species and the parasite’s developmental stages. Because IGF-I exerts pleiotropic effects on the biology of interaction and disease pathogenesis, IGF-I turns up as an attractive tool to explore biological and pathogenic processes underlying infection development. IGF-I pleiotropic effects open further the possibility of approaching IGF-I as a therapeutical target.

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Factors associated with survival in patients with visceral leishmaniasis treated at a reference hospital in northern Minas Gerais - Brazil

Martins,

Paula,

Caldeira

et al. 2024

Rev. Soc. Bras. Med. Trop.

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Association between Insulin-Like Growth Factor-I Levels and the Disease Progression and Anemia in Visceral Leishmaniasis

Cited by 3 publications

References 38 publications

Mathematical Modelling Using Predictive Biomarkers for the Outcome of Canine Leishmaniasis upon Chemotherapy

Mathematical Modelling Using Predictive Biomarkers for the Outcome of Canine Leishmaniasis upon Chemotherapy

Pleiotropic Effect of Hormone Insulin-Like Growth Factor-I in Immune Response and Pathogenesis in Leishmaniases

Factors associated with survival in patients with visceral leishmaniasis treated at a reference hospital in northern Minas Gerais - Brazil

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