The effects of anti-inflammatory agents as host-directed adjunct treatment of tuberculosis in humans: a systematic review and meta-analysis

Hayford, Frank Ekow Atta; Dolman, Robin; Blaauw, R.; Lombard, Martani J; Smuts, Cornelius M.; Malan, Linda; Ricci, Cristian

doi:10.1186/s12931-020-01488-9

Cited by 12 publications

(16 citation statements)

References 56 publications

(251 reference statements)

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“…Vitamin D supplementation along with anti-tubercular drugs regimen also has been found to increase sputum culture conversion rates of MDR TB and reduces relapse rates. 8 Pulmonary tuberculosis is characterized by granuloma formation which is controlled bicellular immune system. Interferon gamma which mediates inflammatory reactions are increased in tubercular infections which in turn have positive correlation with bone fractures.…”

Section: Discussionmentioning

confidence: 99%

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Delayed fracture union in a case of vitamin D dependent rickets associated with pulmonary tuberculosis - a case report

et al. 2021

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Rickets is a defect of bone mineralization caused by vitamin D deficiency, seen most significantly at growth plates that result in radiological bony abnormalities like metaphyseal flaring and cupping, physeal widening with focal and generalised osteomalacia. Here we present a rare case of 7 years old male, a case of vitamin D3 deficiency rickets in a known case of multi drug resistant pulmonary tuberculosis. The patient had suffered left proximal fibular fracture following trivial fall 1.5 month back and had delayed bony union leading to difficulty in walking and pain. The patient was treated with oral vitamin D supplementation. In vitamin D deficiency rickets, there is decreased bone mineralization leading to weak bones and delayed fracture healing in children. Low serum vitamin D levels also caused decreased immunity with increased susceptibility to respiratory infections like pulmonary tuberculosis. Appropriate treatment with injectable or oral vitamin D3 with adequate exposure of sunlight and proper nutrition is the best modality of treatment.

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Section: Discussionmentioning

confidence: 99%

“…It suppresses MHC class 2, interferon gamma and interleukin 2 from CD4 helper T cells. 8 Vitamin D deficiency is seen in 70% of fracture patients. 5…”

Section: Introductionmentioning

confidence: 99%

Delayed fracture union in a case of vitamin D dependent rickets associated with pulmonary tuberculosis - a case report

et al. 2021

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“…NSAIDs have well-known side effects (48). However, as is the case for most other antiinflammatory drugs, no serious adverse effects related to NSAIDs have been reported in clinical trials in TB patients (14,16). Compared to traditional antibiotic treatment, NSAIDs are not subject to bacterial resistance and some may even aid in improving bacterial sensitivity to antibiotics (44).…”

Section: Clinical Trials Investigating the Use Of Cyclooxygenase-inhimentioning

confidence: 99%

“…A recent meta-analysis of clinical trials showed that antiinflammatory medication and pharmaconutrition therapy (vitamin D) may aid in inflammation resolution and improved disease progression outcomes (16). Additionally, the pharmaconutrient omega-3 long-chain PUFA (n-3 LCPUFA) also modify LM production and may be an emerging therapy to consider (17).…”

Section: Introductionmentioning

confidence: 99%

The Manipulation of the Lipid Mediator Metabolism as Adjunct Host-Directed Therapy in Tuberculosis

et al. 2021

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Host-directed therapies (HDTs) enhance the host response to tuberculosis (TB) infection to reduce disease severity. For instance, the manipulation of lipid mediator production diminishes the hyperactive immune response which is a known pathological feature of TB that generates lung tissue damage. Non-steroidal anti-inflammatory drugs (NSAIDs) and omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) are examples of such HDTs. In this mini-review, we recapitulate the literature available on the effects of NSAIDs and n-3 LCPUFA in TB as well as the immunological pathways underpinning these effects. Many NSAIDs have a great deal of data describing their effects and safety and in many jurisdictions are inexpensive, and sold over the counter in neighborhood convenience stores and supermarkets. The potential benefits of NSAIDs in TB are well-documented in pre-clinical studies. The reduction of pro-inflammatory lipid mediator production by inhibiting cyclooxygenase (COX) pathways with NSAIDs has been found to improve lung histopathology, bacterial control, and survival. Additionally, n-3 LCPUFA and its novel bioactive metabolites produced by COX and lipoxygenase (LOX) have been identified as safe and effective pro-resolving and antibacterial pharmaconutrients. Nevertheless, heterogeneous results have been reported in pre-clinical TB studies. Recently, the importance of the correct timing of NSAIDs and n-3 LCPUFA administration in TB has also been highlighted. This mini-review will provide a better understanding of the potential contribution of these therapies toward reducing inflammatory lung damage and improving bactericidal activity, especially during later stages of TB infection. It further highlights that clinical trials are required to confirm benefit and safety in TB patients.

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“…Thus, reducing inflammation may limit tissue damage and improve treatment, and other clinical outcomes (10). Hence, adjunctive TB therapies have been investigated frequently to augment and increase the success of standard TB treatment outcomes via immunomodulation (1,11,12). This host-directed immunotherapeutic treatment concept is designed to address the improvement of long-term outcomes and to promote a cure.…”

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confidence: 99%

Adjunct n-3 Long-Chain Polyunsaturated Fatty Acid Treatment in Tuberculosis Reduces Inflammation and Improves Anemia of Infection More in C3HeB/FeJ Mice With Low n-3 Fatty Acid Status Than Sufficient n-3 Fatty Acid Status

et al. 2021

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Populations at risk for tuberculosis (TB) may have a low n-3 polyunsaturated fatty acid (PUFA) status. Our research previously showed that post-infection supplementation of n-3 long-chain PUFA (LCPUFA) in TB without TB medication was beneficial in n-3 PUFA sufficient but not in low-status C3HeB/FeJ mice. In this study, we investigated the effect of n-3 LCPUFA adjunct to TB medication in TB mice with a low compared to a sufficient n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient (n-3FAD) or n-3 PUFA-sufficient (n-3FAS) diet for 6 weeks before TB infection. Post-infection at 2 weeks, both groups were switched to an n-3 LCPUFA [eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] supplemented diet and euthanized at 4- and 14- days post-treatment. Iron and anemia status, bacterial loads, lung pathology, lung cytokines/chemokines, and lung lipid mediators were measured. Following 14 days of treatment, hemoglobin (Hb) was higher in the n-3FAD than the untreated n-3FAS group (p = 0.022), whereas the n-3FAS (drug) treated control and n-3FAS groups were not. Pro-inflammatory lung cytokines; interleukin-6 (IL-6) (p = 0.011), IL-1α (p = 0.039), MCP1 (p = 0.003), MIP1- α (p = 0.043), and RANTES (p = 0.034); were lower, and the anti-inflammatory cytokine IL-4 (p = 0.002) and growth factor GMCSF (p = 0.007) were higher in the n-3FAD compared with the n-3FAS mice after 14 days. These results suggest that n-3 LCPUFA therapy in TB-infected mice, in combination with TB medication, may improve anemia of infection more in low n-3 fatty acid status than sufficient status mice. Furthermore, the low n-3 fatty acid status TB mice supplemented with n-3 LCPUFA showed comparatively lower cytokine-mediated inflammation despite presenting with lower pro-resolving lipid mediators.

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The effects of anti-inflammatory agents as host-directed adjunct treatment of tuberculosis in humans: a systematic review and meta-analysis

Cited by 12 publications

References 56 publications

Delayed fracture union in a case of vitamin D dependent rickets associated with pulmonary tuberculosis - a case report

Delayed fracture union in a case of vitamin D dependent rickets associated with pulmonary tuberculosis - a case report

The Manipulation of the Lipid Mediator Metabolism as Adjunct Host-Directed Therapy in Tuberculosis

Adjunct n-3 Long-Chain Polyunsaturated Fatty Acid Treatment in Tuberculosis Reduces Inflammation and Improves Anemia of Infection More in C3HeB/FeJ Mice With Low n-3 Fatty Acid Status Than Sufficient n-3 Fatty Acid Status

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