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Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline

Mucosal leishmaniasis (ML) is a severe form of tegumentary leishmaniasis associated with a persistent inflammatory response. High levels of TNF, IFN-γ, CXCL9 and CXCL10 are found in ML patients, and the association of pentoxifylline with antimony is more effective in decreasing the healing time in M...

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Autores principales: Cincura, Carolina, Costa, Rubia S., De Lima, Clara Monica F., Oliveira-Filho, Jamary, Rocha, Paulo Novis, Carvalho, Edgar M., Lessa, Marcus M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696819/
https://www.ncbi.nlm.nih.gov/pubmed/36422934
http://dx.doi.org/10.3390/tropicalmed7110383
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author Cincura, Carolina
Costa, Rubia S.
De Lima, Clara Monica F.
Oliveira-Filho, Jamary
Rocha, Paulo Novis
Carvalho, Edgar M.
Lessa, Marcus M.
author_facet Cincura, Carolina
Costa, Rubia S.
De Lima, Clara Monica F.
Oliveira-Filho, Jamary
Rocha, Paulo Novis
Carvalho, Edgar M.
Lessa, Marcus M.
author_sort Cincura, Carolina
collection PubMed
description Mucosal leishmaniasis (ML) is a severe form of tegumentary leishmaniasis associated with a persistent inflammatory response. High levels of TNF, IFN-γ, CXCL9 and CXCL10 are found in ML patients, and the association of pentoxifylline with antimony is more effective in decreasing the healing time in ML patients when compared to antimony alone. The present study aimed to investigate the existence of a correlation between cytokine and chemokine production and ML severity and evaluate the potential value of cytokine and chemokine production as marker of therapeutic response in ML patients. This prospective study included 86 subjects in an area of endemic Leishmania braziliensis transmission. Patients diagnosed with ML were classified into clinical stages ranging from I to V according to disease severity. TNF, IFN-γ, CXCL9 and CXCL10 levels were quantified in the supernatant of the mononuclear cell cultures by ELISA before and after treatment with antimony alone or antimony plus pentoxifylline. The median TNF level in the group with mild disease (Stages I–II) was 1064 pg/mL (142–3738 pg/mL), while, in the group with moderate or severe disease (Stages III–V), it was 1941 pg/mL (529–5294 pg/mL) (p = 0.008). A direct correlation was observed between ML clinical severity and levels of TNF production (r = 0.44, p = 0.007). Patients who were treated with antimony and pentoxifylline healed significantly faster than those treated with antimony alone (52 vs. 77 days, hazard ratio = 0.60; 95% confidence interval = 0.38–0.95, p = 0.013). Therapeutic failure was higher in the group that received antimony alone (25% vs. 7%; p = 0.041). There was a significant decrease in CXCL9 after therapy of ML in both groups (p = 0.013; p = 0.043). TNF levels are associated with the severity of mucosal diseases, and pentoxifylline associated with antimony should be the recommended therapy for ML in countries where liposomal amphotericin B is not available.
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spelling pubmed-96968192022-11-26 Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline Cincura, Carolina Costa, Rubia S. De Lima, Clara Monica F. Oliveira-Filho, Jamary Rocha, Paulo Novis Carvalho, Edgar M. Lessa, Marcus M. Trop Med Infect Dis Article Mucosal leishmaniasis (ML) is a severe form of tegumentary leishmaniasis associated with a persistent inflammatory response. High levels of TNF, IFN-γ, CXCL9 and CXCL10 are found in ML patients, and the association of pentoxifylline with antimony is more effective in decreasing the healing time in ML patients when compared to antimony alone. The present study aimed to investigate the existence of a correlation between cytokine and chemokine production and ML severity and evaluate the potential value of cytokine and chemokine production as marker of therapeutic response in ML patients. This prospective study included 86 subjects in an area of endemic Leishmania braziliensis transmission. Patients diagnosed with ML were classified into clinical stages ranging from I to V according to disease severity. TNF, IFN-γ, CXCL9 and CXCL10 levels were quantified in the supernatant of the mononuclear cell cultures by ELISA before and after treatment with antimony alone or antimony plus pentoxifylline. The median TNF level in the group with mild disease (Stages I–II) was 1064 pg/mL (142–3738 pg/mL), while, in the group with moderate or severe disease (Stages III–V), it was 1941 pg/mL (529–5294 pg/mL) (p = 0.008). A direct correlation was observed between ML clinical severity and levels of TNF production (r = 0.44, p = 0.007). Patients who were treated with antimony and pentoxifylline healed significantly faster than those treated with antimony alone (52 vs. 77 days, hazard ratio = 0.60; 95% confidence interval = 0.38–0.95, p = 0.013). Therapeutic failure was higher in the group that received antimony alone (25% vs. 7%; p = 0.041). There was a significant decrease in CXCL9 after therapy of ML in both groups (p = 0.013; p = 0.043). TNF levels are associated with the severity of mucosal diseases, and pentoxifylline associated with antimony should be the recommended therapy for ML in countries where liposomal amphotericin B is not available. MDPI 2022-11-16 /pmc/articles/PMC9696819/ /pubmed/36422934 http://dx.doi.org/10.3390/tropicalmed7110383 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cincura, Carolina
Costa, Rubia S.
De Lima, Clara Monica F.
Oliveira-Filho, Jamary
Rocha, Paulo Novis
Carvalho, Edgar M.
Lessa, Marcus M.
Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline
title Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline
title_full Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline
title_fullStr Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline
title_full_unstemmed Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline
title_short Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline
title_sort assessment of immune and clinical response in patients with mucosal leishmaniasis treated with pentavalent antimony and pentoxifylline
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696819/
https://www.ncbi.nlm.nih.gov/pubmed/36422934
http://dx.doi.org/10.3390/tropicalmed7110383
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