Low Serum Levels of Dehydroepiandrosterone and Cortisol in Human Diffuse Cutaneous Leishmaniasis by Leishmania Mexicana

Galindo-Sevilla, Norma; Soto, Norma; Mancilla, Javier; Cérbulo, Arturo; Zambrano, Elena; Chavira, Roberto; Huerto, Jaime

doi:10.4269/ajtmh.2007.76.566

Cited by 18 publications

(11 citation statements)

References 63 publications

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“…The significantly reduced IFN-γ gene expression, and to a lesser extent those of TLR2 and TNF-α, in NK cells of DCL patients, indicates that Leishmania mexicana possibly modulates the host immune response through epigenetic mechanisms. This modulation seems not only related to NK cells since reduced levels of IFN-γ and TNF-α have also been reported in other cells of DCL patients [48] – [50] . It is not clear whether the phenotypical and functional modifications of NK cells are the consequence or the cause of Leishmania infections, yet it is noteworthy that these patients are not prone to other microbial infections.…”

Section: Discussionsupporting

confidence: 54%

NK Cell Activity Differs between Patients with Localized and Diffuse Cutaneous Leishmaniasis Infected with Leishmania mexicana: A Comparative Study of TLRs and Cytokines

et al. 2014

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Leishmania mexicana causes localized (LCL) or diffuse cutaneous leishmaniasis (DCL). The cause of dissemination in DCL remains unknown, yet NK cells possibly play a role in activating leishmanicidal mechanisms during innate and adaptive immune responses. We had previously shown that Leishmania lipophosphoglycan (LPG) is a ligand for TLR2, activating human NK cells. We have now analyzed NK cells in LCL and DCL patients. NK numbers and effector mechanisms differed drastically between both groups of patients: DCL patients showed reduced NK cell numbers; diminished IFN-γ and TNF-α production; and lower TLR2, TLR1, and TLR6 expression as compared to LCL patients. The altered protein expression found in NK cells of DCL patients correlated with their down-regulation of IFN-γ gene expression in LPG-stimulated and non-stimulated cells as compared to LCL patients. NK cell response was further analyzed according to gender, age, and disease evolution in LCL patients showing that female patients produced higher IFN-γ levels throughout the disease progression, whereas TLR2 expression diminished in both genders with prolonged disease evolution and age. We furthermore show the activation pathway of LPG binding to TLR2 and demonstrated that TLR2 forms immunocomplexes with TLR1 and TLR6. In addition to the reduced NK cell numbers in peripheral blood, DCL patients also showed reduced NK cell numbers in the lesions. They were randomly scattered within the lesions, showing diminished cytokine production, which contrasts with those of LCL lesions, where NK cells produced IFN-γ and TNF-α and were found within organized granulomas. We conclude that in DCL patients the reduced NK-cell numbers and their diminished activity, evidenced by low TLR expression and low cytokine production, are possibly involved in the severity of the disease. Our results provide new information on the contribution of NK cells in Leishmania infections of the human host.

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Section: Discussionsupporting

confidence: 54%

NK Cell Activity Differs between Patients with Localized and Diffuse Cutaneous Leishmaniasis Infected with Leishmania mexicana: A Comparative Study of TLRs and Cytokines

et al. 2014

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“…There is only one study addressing an immune-endocrine imbalance in human leishmaniasis (Gallindo-Sevilla et al, 2007); this study found lower serum levels of DHEA and cortisol in diffuse cutaneous leishmaniasis (DCL) patients compared with LCL patients or healthy volunteers. When DCL patients were excluded from the study, there was a statistically significant reduction of DHEA in LCL patients compared to age-matched controls.…”

Section: Discussionmentioning

confidence: 80%

“…Stress, gender and age can influence disease outcome in mice and hamsters (Alexander, 1988;Travi et al, 2002;Ruiz et al, 2003;Ehrchen et al, 2004), and hormonal changes have been described in patients infected with L. mexicana (Gallindo-Sevilla et al, 2007). Changes in plasma hormone levels have been correlated with an imbalanced cytokine profile in several acute and chronic infections (Reincke et al, 1998;Bhasin et al, 2001;Leal et al, 2003Leal et al, , 2006Mavoungou et al, 2005;Libonati et al, 2006;Del Rey et al, 2007;Gallindo-Sevilla et al, 2007;Pinto et al, 2007). Hormone level changes have also been implicated in the establishment of human malaria (Kurtis et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Hormone levels are associated with clinical markers and cytokine levels in human localized cutaneous leishmaniasis

Baccan

Oliveira

Sousa

et al. 2011

Brain, Behavior, and Immunity

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Leishmaniasis is a serious health problem in several parts of the world, and localized cutaneous leishmaniasis (LCL) is the most frequent presentation of the tegumentary form of this disease cluster. Clinical presentations of leishmaniasis are influenced by both parasite and host factors, with emphasis on the host immune response. Alterations in plasma hormone levels have been described in many infections, and changes in hormone levels could be related to an imbalanced cytokine profile. In the present work, we evaluated a group of patients with LCL to determine changes in plasma hormone levels (cortisol, DHEA-S, estradiol, prolactin and testosterone) and their association with clinical markers of disease (lesion size, dose used to reach cure and time to cure) and with cytokines produced by PBMC stimulated by SLA (IFN-γ, IL-10 and TNF-α). Individuals with LCL exhibited lower plasma levels of DHEA-S, prolactin and testosterone compared with sex-matched controls, whereas levels of cortisol and estradiol were similar between patients and controls. Plasma levels of cortisol, estradiol or prolactin positively correlated with at least one clinical parameter. Cortisol and prolactin levels exhibited a negative correlation with levels of IFN-γ, whereas no correlation was observed with IL-10 or TNF-α levels. A decrease in DHEA-S levels was observed in male LCL patients when compared to male healthy controls. No other differences between the sexes were observed. Our results indicate a role for neuroendocrine regulation that restricts Th1 responses in human LCL. It is possible that, although impairing parasite killing, such neuroimmunomodulation may contribute to limiting tissue damage.

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“…Briefly, after paraffin removal, the sections (5 lm thick) were rehydrated in PBS for 30 min at room temperature. Then the sections were preincubated with 5% bovine serum albumin for 60 min, and then incubated overnight at 4°C in a humidified chamber with a 1:500 dilution of patient serum from a 55-year-old man who had suffered from DL for 16 years (Galindo-Sevilla et al 2007). It was determined by Western blot analysis of promastigote or amastigote lysates that the serum of this patient had an antibody titer greater than…”

Section: Immunohistology Of Tissues From Infected Micementioning

confidence: 99%

Effect of Ambient Temperature on the Clinical Manifestations of Experimental Diffuse Cutaneous Leishmaniasis in a Rodent Model

Quiñonez-Díaz

Mancilla-Ramı́rez

Avila-García

et al. 2012

Vector-Borne and Zoonotic Diseases

Self Cite

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Dermal species of Leishmania have a relatively broad temperature range for optimal growth in vitro, with temperature differences accompanied by a form change. This suggests that when the host is living in moderate temperatures (22°C), infection may proceed at temperatures lower than those that occur in tropical regions (32°C), and a different clinical expression of the disease due to a different parasitic form may result. The aim of this study was to investigate the effect of environmental temperature on the clinical expression of the disease. BALB/C mice infected with Leishmania mexicana were housed at 32°±2°C or 22°±1°C, and assessed for the development of inflammation and the presence of parasites in organs using PCR and immunohistology. The clinical expression of leishmaniasis at 32°C included inflammation at the site of inoculation with swelling of the nose and tail, whereas at 22°C, up to 50% of the infected mice developed dry exfoliative dermatitis with alopecia on the dorsum. In both cases, parasite colonization was confirmed in the skin, with parasites at more external locations at 22°C. Parasite visceralization was confirmed in all internal organs and glands in both cases based on PCR and immunohistology. In conclusion, the clinical expression of diffuse leishmaniasis by Leishmania mexicana in laboratory mice is modified by temperature, from nodular inflammation at 32°C, to dry exfoliative dermatitis and alopecia at 22°C, with parasite visceralization in both cases.

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Low Serum Levels of Dehydroepiandrosterone and Cortisol in Human Diffuse Cutaneous Leishmaniasis by Leishmania Mexicana

Cited by 18 publications

References 63 publications

NK Cell Activity Differs between Patients with Localized and Diffuse Cutaneous Leishmaniasis Infected with Leishmania mexicana: A Comparative Study of TLRs and Cytokines

NK Cell Activity Differs between Patients with Localized and Diffuse Cutaneous Leishmaniasis Infected with Leishmania mexicana: A Comparative Study of TLRs and Cytokines

Hormone levels are associated with clinical markers and cytokine levels in human localized cutaneous leishmaniasis

Effect of Ambient Temperature on the Clinical Manifestations of Experimental Diffuse Cutaneous Leishmaniasis in a Rodent Model

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