UMMS Affiliation
Department of Medicine, Division of Pulmonary, Allergy And Critical Care Medicine
Publication Date
2018-07-25
Document Type
Article
Disciplines
Bacterial Infections and Mycoses | Immunology and Infectious Disease | Infectious Disease | Microbiology | Nutritional and Metabolic Diseases | Therapeutics
Abstract
BACKGROUND: Matrix metalloproteinases (MMPs) are considered to be key mediators of tuberculosis (TB) pathology but their role in tuberculosis - diabetes comorbidity (TB-DM) is not well understood.
METHODS: To study the association of MMP levels with severity and extent of disease as well as bacterial burden in TB-DM, we examined the systemic levels of MMP-1, - 2, - 3, - 7, - 8, - 9, - 10, - 12 and - 13 in individuals with TB-DM and compared them to those with TB alone (TB) or healthy controls (HC). RESULTS: Circulating levels of MMP-1, - 2, - 3, - 7, - 10 and - 12 were significantly higher in TB-DM compared to both TB and HC and MMP -13 levels were higher in comparison to HC alone. To understand the effect of standard anti-tuberculosis therapy (ATT) on these MMP levels in TB-DM, we measured the levels of MMPs at the end of treatment (post-treatment). Our findings indicate that ATT is associated with a significant reduction in the levels of MMP-1, - 2, - 3, - 8 and - 13 post-treatment. Moreover, the levels of MMP-1, - 2, - 3, - 9 and - 12 were significantly higher in TB-DM individuals with cavitary disease and/or bilateral disease at baseline but not post-treatment. Similarly, the levels of MMP -1, - 2, - 3 and - 8 exhibited a significant positive relationship with bacterial burden and HbA1c levels at baseline but not post-treatment. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited significantly higher levels of MMP-1, - 2, - 10 and - 12 at baseline and of MMP-1 and -3 post-treatment compared to those newly diagnosed with DM (NDM). Finally, KDM individuals on metformin treatment exhibited significantly lower levels of MMP-1, - 2, - 3, - 7, - 9 and - 12 at baseline and of MMP-7 post-treatment. CONCLUSIONS: Our data demonstrate that systemic MMP levels reflect baseline disease severity and extent in TB-DM, differentiate KDM from NDM and are modulated by ATT and metformin therapy.
Keywords
Diabetes mellitus, Matrix metalloproteinases, Mycobacterium tuberculosis
Rights and Permissions
© The Author(s). 2018 Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI of Published Version
10.1186/s12879-018-3246-y
Source
BMC Infect Dis. 2018 Jul 25;18(1):345. doi: 10.1186/s12879-018-3246-y. Link to article on publisher's site
Journal/Book/Conference Title
BMC infectious diseases
Related Resources
PubMed ID
30045688
Repository Citation
Kumar, Nathella P.; Moideen, Kadar; Viswanathan, Vijay; Shruthi, Basavaradhya S.; Sivakumar, Shanmugam; Menon, Pradeep A.; Kornfeld, Hardy; and Babu, Subash, "Elevated levels of matrix metalloproteinases reflect severity and extent of disease in tuberculosis-diabetes co-morbidity and are predominantly reversed following standard anti-tuberculosis or metformin treatment" (2018). Open Access Articles. 3553.
https://escholarship.umassmed.edu/oapubs/3553
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Bacterial Infections and Mycoses Commons, Immunology and Infectious Disease Commons, Infectious Disease Commons, Microbiology Commons, Nutritional and Metabolic Diseases Commons, Therapeutics Commons