Increased levels of cortisol are associated with the severity of experimental visceral leishmaniasis in a Leishmania (L.) infantum-hamster model

Autor: Adriano Gomes-Silva, Eduardo Fonseca Pinto, Vinicius F. Carvalho, Andrea Franco Saavedra, Alda Maria Da-Cruz, Luzinei da Silva-Couto, Milla Bezerra-Paiva, Tayany de D. Barros-Gonçalves, Raquel Peralva Ribeiro-Romão
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Hydrocortisone
Physiology
RC955-962
Biochemistry
Cortisol
Medical Conditions
Transforming Growth Factor beta
Cricetinae
Zoonoses
Immune Physiology
Arctic medicine. Tropical medicine
Leukocytes
Medicine and Health Sciences
Medicine
Lipid Hormones
Leishmania infantum
Leishmaniasis
Mammals
Protozoans
Leishmania
Innate Immune System
biology
Interleukin
Eukaryota
Radioimmunoassay
Arginase
Infectious Diseases
Vertebrates
Hamsters
Leishmaniasis
Visceral
Cytokines
Public aspects of medicine
RA1-1270
Research Article
Neglected Tropical Diseases
medicine.medical_specialty
Immunology
Hamster
Rodents
Parasite Replication
Internal medicine
parasitic diseases
Parasitic Diseases
Animals
Humans
Glucocorticoids
Steroid Hormones
Protozoan Infections
Mesocricetus
business.industry
Interleukins
Public Health
Environmental and Occupational Health
Organisms
Biology and Life Sciences
Molecular Development
medicine.disease
biology.organism_classification
Tropical Diseases
Hormones
Parasitic Protozoans
Visceral leishmaniasis
Endocrinology
Immune System
Amniotes
Parasitology
business
Zoology
Spleen
Developmental Biology
Zdroj: PLoS Neglected Tropical Diseases, Vol 15, Iss 11, p e0009987 (2021)
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
1935-2727
Popis: Background Several infectious diseases are associated with hypothalamic-pituitary-adrenal (HPA) axis disorders by elevating circulating glucocorticoids (GCs), which are known to have an immunosuppressive potential. We conducted this study in golden hamsters, a suitable model for human visceral leishmaniasis (VL), to investigate the relationship of Leishmania (L.) infantum infection on cortisol production and VL severity. Methods L. infantum-infected (n = 42) and uninfected hamsters (n = 30) were followed-up at 30, 120, and 180 days post-infection (dpi). Plasma cortisol was analyzed by radioimmunoassay and cytokines, inducible nitric oxide synthase (iNOS), and arginase by RT-qPCR. Results All hamsters showed splenomegaly at 180 dpi. Increased parasite burden was associated with higher arginase expression and lower iNOS induction. Cortisol levels were elevated in infected animals in all-time points evaluated. Except for monocytes, all other leucocytes showed a strong negative correlation with cortisol, while transaminases were positively correlated. Immunological markers as interleukin (IL)-6, IL-1β, IL-10, and transforming growth-factor-β (TGF-β) were positively correlated to cortisol production, while interferon-γ (IFN-γ) presented a negative correlation. A network analysis showed cortisol as an important knot linking clinical status and immunological parameters. Conclusions These results suggest that L. infantum increases the systemic levels of cortisol, which showed to be associated with hematological, biochemical, and immunological parameters associated to VL severity.
Author summary Visceral leishmaniasis (VL) is an infectious disease that is common in most tropical countries. VL has high morbidity and leads to death if not properly treated. In Brazil, Leishmania (Leishmania) infantum is the main causative agent of VL. Golden hamsters have proven to be a suitable model for VL. Despite the importance of hypothalamic-pituitary-adrenal (HPA) axis disturbances in infectious disease, few studies have addressed this issue in VL. In this study, we showed that L. infantum-infected hamsters present augmented levels of plasmatic cortisol in association with increased spleen parasite burden. Indeed, a strong positive correlation was observed between cortisol and biochemical parameters (AST/ALT/ALP) related to liver damage, as well as pro-inflammatory cytokines (IL-6 and IL-1β), anti-inflammatory cytokines (IL-10 and TGF-β), and the arginase enzyme that may favor the progression of infection. On the other side, cortisol was negatively correlated with leucocytes, except monocytes, and with IFN-γ and iNOS, which are involved in parasite-killing macrophage function. These results shed light on an unexplored aspect of VL pathogenesis, which is the importance of cortisol production in the disease-associated immune dysfunction.
Databáze: OpenAIRE
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