Skip to main content

Higher plasma interleukin − 6 levels are associated with lung cavitation in drug-resistant tuberculosis



Lung cavitation is associated with heightened TB transmission and poor treatment outcomes. This study aimed to determine the relationship between systemic inflammation and lung cavitation in drug-resistant TB patients with and without HIV co-infection.


Plasma samples were obtained from 128 participants from the CAPRISA 020 Individualized M(X)drug-resistant TB Treatment Strategy Study (InDEX) prior to treatment initiation. Lung cavitation was present in 61 of the 128 drug-resistant TB patients with 93 being co-infected with HIV. The plasma cytokine and chemokine levels were measured using the 27-Plex Human Cytokine immunoassay. Modified Poisson regression models were used to determine the association between plasma cytokine/chemokine expression and lung cavitation in individuals with drug-resistant TB.


Higher Interleukin-6 plasma levels (adjusted risk ratio [aRR] 1.405, 95% confidence interval [CI] 1.079–1.829, p = 0.011) were associated with a higher risk of lung cavitation in the multivariable model adjusting for age, sex, body mass index, HIV status, smoking and previous history of TB. Smoking was associated with an increased risk of lung cavitation (aRR 1.784, 95% CI 1.167–2.729, p = 0.008). An HIV positive status and a higher body mass index, were associated with reduced risk of lung cavitation (aRR 0.537, 95% CI 0.371–0.775, p = 0.001 and aRR 0.927, 95% CI 0.874–0.983, p = 0.012 respectively).


High plasma interleukin-6 levels are associated with an increased risk of cavitary TB highlighting the role of interleukin-6 in the immunopathology of drug-resistant TB.

Peer Review reports


Lung cavitation is a key pathological feature of Mycobacterium tuberculosis (Mtb) infection that results in extensive caseous necrosis. Lung cavities are pathologic gas-filled spaces in lung parenchyma associated with a high bacterial burden resulting in increased transmission, poor drug penetration, and increased morbidity and mortality in people with tuberculosis (TB) [1].

While the mechanism by which cavities are formed is unknown, they are thought to be a consequence of a complex host-pathogen interaction, involving various biochemical, biophysical, microbiological and immunological processes [1]. Data on immunological drivers remain limited, although the inflammatory processes that drive cell necrosis rather than apoptosis during Mtb infection are thought to play a key role in cavity formation [2, 3]. Lung cavitation has several negative consequences for the patient including increased symptom burden, poor drug penetration, longer time to culture conversion, poor treatment outcomes, increased risk of relapse, long-term respiratory impairment, reduced quality of life, and an increased risk for the development of drug resistance [1, 4,5,6]. Cavitation is shown to promote development of drug resistance in multiple ways, including increasing the frequency of replication-induced mutations [7, 8] through high rates of bacterial proliferation as well as through poor penetration of antimicrobial drugs resulting in pharmacokinetic-pharmacodynamic mismatch [9]. Drug-resistant TB is a major driver of TB related mortality in sub-Saharan Africa, where the incidence of DR-TB is rising. Within sub-Saharan Africa, South Africa has the highest prevalence of multidrug-resistant (MDR)-TB and has recorded the largest outbreak of extensively drug-resistant (XDR)-TB ever reported [10]. Treatment outcomes for DR-TB remain poor, with reports from SA revealing a 70% mortality rate and treatment cure/completion of only 11% after 60 months of follow-up in XDR-TB patients [11]. The presence of lung cavities leads to an increased risk of developing XDR-TB, even among MDR-TB patients on directly observed therapy [12].

The current TB treatment regimens have multiple challenges, including high pill burdens, drug toxicities, prolonged treatment duration and adherence challenges [13]. New approaches to control TB are needed for both diagnosis and treatment, with host-directed therapies being a promising treatment strategy for TB [14]. Identifying blood biomarkers of disease severity and treatment outcome could represent a cost-effective method to personalise treatment and improve treatment outcome. We have previously identified several inflammatory markers associated with TB risk in HIV positive, antiretroviral therapy (ART) experienced individuals (specifically lipopolysaccharide binding protein (LBP), intercellular adhesion molecule (ICAM) -1, interleukin (IL) -1β, IL-6 and IL-1Ra) [15, 16] as well as inflammatory markers associated with disease severity (measured by presence of lung cavitation) in drug-susceptible pulmonary TB (including IL-6 and IL-1Ra) [17]. Here we utilised biological specimens from a well characterised cohort with comprehensive clinical and demographic data to characterise immune markers of lung cavitation in MDR/XDR-TB patients.

Materials and methods

Study participants

The study aimed to characterise biomarkers of lung cavitation in MDR/XDR-TB patients and was performed utilising stored plasma specimens from the CAPRISA 020 Individualized M(X)drug-resistant TB Treatment Strategy Study (InDEX). The InDEX study was a randomized controlled clinical trial assessing if a gene-derived individualised treatment approach in patients with drug-resistant TB improved treatment success. Enrolled InDEX study participants were recruited to King Dinuzulu Hospital (KDH) in KwaZulu-Natal, South Africa following a confirmed diagnosis of drug-resistant TB. The presence of lung cavitation was determined by postero-anterior chest radiograph unless a chest radiograph performed 14 days prior to the date of screening was available for review. Study participants were > 18 years with pulmonary TB and Xpert MTB/RIF evidence of rifampicin resistance. For this sub-study, 128 available plasma samples at baseline prior to treatment initiation were evaluated.

Sample collection and processing

Peripheral blood was collected in acid citrate dextrose (ACD) tubes. Plasma was separated by centrifugation (1600 rpm for 10’) and cryopreserved at − 80 °C until use.

Cytokine/Chemokine measurement

Cryopreserved plasma samples were thawed and mixed before performing the assays. Cytokine/Chemokine levels were be measured using the Pro Human Cytokine 27-Plex Assay (Bio-Rad, USA) that covers major inflammatory cytokines and analysed on a BioPlex-200 system (Bio-Rad). The Human Cytokine/Chemokine Panel includes the following cytokines and chemokines: fibroblast growth factor (FGF) basic, eotaxin, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), interleukin (IL) -1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17 A, interferon γ–Inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP) -1α, MIP-1β, platelet-derived growth factor (PDGF) -BB, regulated on activation normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF) -α, Vascular endothelial growth factor (VEGF). All assays were performed following manufacturers’ instructions. Samples with values below the limit of detection (LOD) were assigned the value half of the LOD (LOD/2) in pg/mL.

Statistical analyses

Statistical analyses were performed using IBM SPSS Statistics version 25, R software version 4.2.2 and the graphs made using GraphPad Prism (V9). All cytokines/chemokines with more than 60% of samples above the limit of detection were log-transformed to reduce variance (IL-1Ra, IL-4, IL-6, IL-7, IL-8, IL-9, IL-13, G-CSF, MCP-1, FGF basic, MIP-1α, MIP-1β, TNF-α, PDGF-BB, Eotaxin, IP-10, RANTES). Cytokines/chemokines with less than 60% detectability were analysed as binary variables (IL-1β, IL-10, IL-12, IL-17, VEGF, GM-CSF, IFN-γ) while cytokines with less than 10% of samples detectable (IL-5, IL-15, IL-2) were excluded from the multivariable analysis to avoid quasi-complete separation. To determine the association between plasma cytokine expression at baseline with disease severity measured by lung cavitation, univariable and multivariable modified Poisson regression models were used. The presence of lung cavitation at baseline was the outcome. Multivariable analyses adjusted for clinical and demographic variables which included age, sex, HIV status, smoking, BMI and history of previous TB. In addition, the use of antiretroviral therapy (ART) was adjusted for when analysing HIV-infected individuals. The association between covariates adjusted for in the multivariable models with lung cavitation was also assessed using modified Poisson regression models.


Participant characteristics

The demographic and clinical characteristics of study participants are described in Table 1. The median age was 35 years (IQR 29–41.2), with 57% (73/128) being males. The median body mass index (BMI) was 20.2 kg/m2 (IQR 18.5–22.7). Participants with rifampicin-resistant TB and MDR-TB accounted for 89.84% (115/128) of the total cohort while participants with Pre-XDR/XDR-TB accounted for 10.16% (13/128). HIV co-infection was present in 73% (93/128) of study participants with 90.32% (84/93) receiving antiretroviral therapy (ART). The presence of lung cavitation was observed among 47.67% (61/128) of study participants.

Table 1 Demographic and clinical characteristics of participants

Effect of plasma cytokine/chemokine expression on presence of lung cavitation

Modified Poisson regression models were used to assess the association between plasma cytokine/chemokine expression and lung cavitation in individuals with DR-TB. Following univariable and multivariable analyses adjusting for age, sex, BMI, HIV status, smoking and previous history of TB; increased plasma expression of IL-6 [aRR 1.405, 95% CI 1.079–1.829, p = 0.011] was associated with an increased risk of lung cavitation in the total cohort. A unit increase in the log expression of IL-6 led to a 41% increase in the risk of lung cavitation (Table 2). Similarly, a trend was observed in the sub-analysis of HIV positive participants controlling for ART use [aRR 1.424, 95% CI 0.991–2.046, p = 0.056 (Additional File 1).

Multivariable models that fitted lung cavitation against the adjusted variables (age, sex, BMI, HIV status, smoking and previous history of TB) in the total cohort, showed that HIV positive participants had a significant 46% reduction in the risk of lung cavitation in comparison to HIV negative participants [aRR 0.536, 95% CI 0.371–0.775, p = 0.001]. The risk of lung cavitation was 7% lower for each unit increase in BMI [aRR 0.927, 95% CI 9.874–0.983, p = 0.012] while males had a 44% lower risk of lung cavitation [aRR 0.559, 95% CI 0.381–0.821, p = 0.003]. Smoking was associated with an increased risk of lung cavitation [aRR 1.784, 95% CI 1.167–2.729, p = 0.008] (Additional File 1).

Table 2 Association between plasma cytokine/chemokine expression with lung cavitation among HIV positive and negative participants with DR-TB (n = 125)


Cavitary TB is a serious consequence of pulmonary TB, and is associated with increased morbidity and mortality, the development of drug resistance and higher transmission rates [1]. In this study, we assessed the association between plasma cytokine/chemokine expression and lung cavitation among individuals with DR-TB. Increased plasma expression of IL-6 was associated with higher risk of lung cavitation among individuals with DR-TB. HIV positive participants, males and participants with higher BMI had a reduced risk of lung cavitation in participants with DR-TB. Additionally, Individuals who smoke had an increased risk of lung cavitation.

IL-6 is a pleiotropic cytokine with dual pro- and anti-inflammatory properties. IL-6 activates target cells either via membrane–bound IL-6R (classic signalling) or through soluble forms of IL-6R (sIL-6R, trans-signalling), the latter of which was shown to account for its proinflammatory properties [18]. IL-6 modulates innate and adaptive immunity [19]. It is secreted by various immune cells including macrophages, neutrophils and lung epithelial cells at sites of inflammation. IL-6, is induced by Mtb infection, [20] and has both positive and negative effects on host immune control of Mtb [21]. We have previously shown that plasma IL-6 is associated with both shorter time to culture conversion as well as increased risk of TB recurrence and presence of lung cavitation in patients with drug susceptible TB, highlighting its dual role in TB [15, 16]. Increased IL-6 levels measured in bronchoalveolar lavage (BAL) of patients with pulmonary TB were shown to correlate with lung cavitation [22]. Additionally, BAL IL-6 expression has previously been correlated with a chest high-resolution computed tomography score which factored cavities, miliary nodules and bronchial wall thickening among HIV negative patients with active TB [22]. IL-6 has also been implicated in promoting fibroblast development and subsequently, pulmonary fibrosis [23, 24]. Elevated IL-6 expression was also reported in pleural fluid of TB patients as well as in cerebrospinal fluid (CSF) in patients with TB meningitis [25,26,27]. While IL-6 is predominantly associated with disease severity in TB, knockout studies have shown that IL-6 plays an important role in controlling bacterial load early in the infection through induction of protective interferon gamma-producing T cell responses [28].

The COVID-19 pandemic has highlighted the use of host directed therapies targeting IL-6. This includes biological agents that target the IL-6 itself (clazakizumab, olokizumab, sirukumab and siltuximab), its receptor (tocilizumab and sarilumab) and drugs that inhibit IL-6 trans-signalling by blocking the soluble IL-6 receptor (sIL-6R) (olamkicept) [29, 30]. These IL-6 inhibitors vary in potency, have distinct pharmacodynamics and result in distinct downstream effects. While cytokine and receptor blockers are known to inhibit the classic IL-6 pathway and result in significant immunosuppression, the sIL-6R inhibitor, olamkicept was shown to exclusively block IL-6 proinflammatory trans-signalling without affecting IL-6 classic signalling and causing immunosuppression [30]. As seen with the use of IL-6 targeting in COVID-19, the efficacy of any IL-6 therapy would depend on the severity of the disease and the timing of the intervention; as well as the ability to distinguish between IL-6 as a cause or a consequence of the disease.

Smoking was found to increase the risk of lung cavitation among DR-TB patients. Smoking is known to be associated with more extensive lung disease and cavitation as well as poor treatment outcome in pulmonary TB [31, 32]. HIV status, increased BMI and male sex were associated with reduced risk of lung cavitation. Previous studies have reported lower odds of lung cavitation in HIV positive individuals with pulmonary TB in comparison to HIV negative individuals and this was related to immunosuppression and the reduction in CD4+ T cell counts that are thought to play a key role in lung immunopathology during Mtb infection [33,34,35,36]. In addition to lower prevalence of cavitary disease HIV positive individuals are more likely to have acid-fast smear negative disease, as well as to have extrapulmonary TB, all of which are associated with delays in TB diagnosis and poor treatment outcomes [37,38,39]. Higher odds of lung cavitation were reported among TB cases with severe malnutrition (BMI < than 16 kg/m2) in comparison to individuals with a BMI greater than or equal than 18.5 kg/m2 [40]. Weight loss is a clinical manifestation of TB and is known to increase following TB treatment [41] however, a lack of adherence to MDR-TB treatment leads to slower increases in BMI [42]. Contrasting results have been reported on the relationship between gender and TB disease severity. Greater lung involvement was reported in males in comparison to females with pulmonary TB using Ralph scoring [43] with pulmonary fibrosis also being more frequent among males in comparison to females [44]. The relationship between gender and lung cavitation among drug-resistant TB patients remains to be further characterised.

Previous studies have highlighted the role of IL-6 in drug-susceptible TB, however studies on cytokine signatures and their role in DR-TB are limited. Here we highlight the association between plasma IL-6 levels and presence of lung cavitation in a well-characterised cohort of individuals with active DR-TB. This study has several limitations, including a lack of access to viral load and CD4 counts for HIV positive individuals with DR-TB at sampling timepoint. Additionally, we were not able to determine whether the lung cavitation was related to previous TB disease or the current episode of TB. While our results show an association between plasma IL-6 and presence of cavitary disease in DR-TB, we are unable to distinguish between IL-6 as a consequence or a cause of the disease. Further studies are needed to determine the relationship between lung cavitation and IL-6 signalling and the potential of IL-6 blocking agents in TB treatment.

Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.



Acid citrate dextrose


Adjusted risk ratio


Antiretroviral therapy


Bronchoalveolar lavage


Body mass index


Centre for the AIDS Programme of Research in South Africa


Confidence interval


Cerebrospinal fluid


Drug resistant tuberculosis


Fibroblast growth factor


Granulocyte colony-stimulating factor


Granulocyte-macrophage colony-stimulating factor


Human immunodeficiency virus


Intercellular adhesion molecule-1


Interferon gamma




The Individualized M(X) drug-resistant TB treatment Strategy Study


Interferon gamma-induced protein 10


Interquartile range


King Dinuzulu hospital


lypopolysaccharide binding protein


Limit od detection


Monocyte chemoattractant protein-1




Macrophage inflammatory protein


Mycobacterium tuberculosis


Platelet-derived growth factor-BB


Regulated on activation, normal T cell expressed and secreted


Risk ratio




Tumor necrosis factor


Vascular endothelial growth factor


Extensively drug-resistant TB


  1. Urbanowski ME, Ordonez AA, Ruiz-Bedoya CA, Jain SK, Bishai WR. Cavitary tuberculosis: the gateway of disease transmission. Lancet Infect Dis (2020).

  2. Ravimohan S, Kornfeld H, Weissman D, Bisson GP. Tuberculosis and lung damage: from epidemiology to pathophysiology. Eur Respiratory Rev 27 (2018).

  3. Dheda K, et al. Lung remodeling in pulmonary tuberculosis. J Infect Dis. 2005;192:1201–10.

    Article  CAS  PubMed  Google Scholar 

  4. Hernandez-Romieu AC et al. in Open Forum Infectious Diseases. ofz232 (Oxford University Press US).

  5. Gadkowski LB, Stout JE. Cavitary pulmonary disease. Clin Microbiol Rev. 2008;21:305–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhang L, et al. Risk factors for pulmonary cavitation in tuberculosis patients from China. Emerg Microbes Infections. 2016;5:1–11.

    Google Scholar 

  7. Kempker RR, et al. Additional drug resistance in Mycobacterium tuberculosis isolates from resected cavities among patients with multidrug-resistant or extensively drug-resistant pulmonary tuberculosis. Clin Infect Dis. 2012;54:e51–4.

    Article  CAS  PubMed  Google Scholar 

  8. Howard W, Maresh F, Mueller E, Yannitelli S, Woodruff C. The role of pulmonary cavitation in the development of bacterial resistance to streptomycin. Am Rev Tuberculosis. 1949;59:391–401.

    CAS  Google Scholar 

  9. Moreno-Gamez S, et al. Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance. Proc Natl Acad Sci. 2015;112:E2874–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wallengren K, et al. Drug-resistant tuberculosis, KwaZulu-Natal, South Africa, 2001–2007. Emerg Infect Dis. 2011;17:1913.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Pietersen E, et al. Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study. The Lancet. 2014;383:1230–9.

    Article  Google Scholar 

  12. Dheda K, et al. Drug-penetration gradients associated with acquired drug resistance in patients with tuberculosis. Am J Respir Crit Care Med. 2018;198:1208–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kolloli A, Subbian S. Host-directed therapeutic strategies for tuberculosis. Front Med. 2017;4:171.

    Article  Google Scholar 

  14. Tobin DM. Host-directed therapies for tuberculosis. Cold Spring Harbor Perspectives in Medicine. 2015;5:a021196.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Pillay K, et al. Plasma biomarkers of risk of tuberculosis recurrence in HIV co-infected patients from South Africa. Front Immunol. 2021;12:907.

    Article  Google Scholar 

  16. Sivro A, et al. Plasma cytokine predictors of tuberculosis recurrence in antiretroviral-treated HIV-infected individuals from Durban, South Africa. Clinical Infectious Diseases; 2017.

  17. Rambaran S, et al. Effect of inflammatory Cytokines/Chemokines on Pulmonary Tuberculosis Culture Conversion and Disease Severity in HIV-Infected and-uninfected individuals from South Africa. Front Immunol. 2021;12:1123.

    Article  Google Scholar 

  18. Garbers C, Heink S, Korn T, Rose-John S. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discovery. 2018;17:395–412.

    Article  CAS  PubMed  Google Scholar 

  19. Choy E, Rose-John S. Interleukin-6 as a multifunctional regulator: inflammation, immune response, and fibrosis. J Scleroderma Relat Disorders. 2017;2:1–S5.

    Article  Google Scholar 

  20. Singh PP, Goyal A. Interleukin-6: a potent biomarker of mycobacterial infection. Springerplus. 2013;2:1–8.

    Article  Google Scholar 

  21. Boni FG, Hamdi I, Koundi LM, Shrestha K, Xie J. Cytokine storm in tuberculosis and IL-6 involvement. Infect Genet Evol. 2022;97:105166.

    Article  CAS  PubMed  Google Scholar 

  22. Casarini M, et al. Cytokine levels correlate with a radiologic score in active pulmonary tuberculosis. Am J Respir Crit Care Med. 1999;159:143–8.

    Article  CAS  PubMed  Google Scholar 

  23. Moodley YP, et al. Fibroblasts isolated from normal lungs and those with idiopathic pulmonary fibrosis differ in interleukin-6/gp130-mediated cell signaling and proliferation. Am J Pathol. 2003;163:345–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6:a016295.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wong C-f, et al. Assay of pleural fluid interleukin-6, tumour necrosis factor-alpha and interferon-gamma in the diagnosis and outcome correlation of tuberculous effusion. Respir Med. 2003;97:1289–95.

    Article  PubMed  Google Scholar 

  26. Rohlwink UK, et al. Biomarkers of cerebral injury and inflammation in pediatric tuberculous meningitis. Clin Infect Dis. 2017;65:1298–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Teunissen CE, Rohlwink U, Pajkrt D, Naudé PJ. Biomarkers of tuberculous meningitis and Pediatric Human Immunodeficiency Virus on the african continent. Front Neurol. 2022;13:793080.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Saunders BM, Frank AA, Orme IM, Cooper AM. Interleukin-6 induces early gamma interferon production in the infected lung but is not required for generation of specific immunity to Mycobacterium tuberculosis infection. Infect Immun. 2000;68:3322–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Choy EH, et al. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol. 2020;16:335–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schreiber S, et al. Therapeutic Interleukin-6 trans-signaling inhibition by Olamkicept (sgp130Fc) in patients with active inflammatory bowel disease. Gastroenterology. 2021;160:2354–66. e2311.

    Article  CAS  PubMed  Google Scholar 

  31. Bai K-J, Lee J-J, Chien S-T, Suk C-W, Chiang C-Y. The influence of smoking on pulmonary tuberculosis in diabetic and non-diabetic patients. PLoS ONE. 2016;11:e0156677.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Leung CC, et al. Smoking adversely affects treatment response, outcome and relapse in tuberculosis. Eur Respir J. 2015;45:738–45.

    Article  PubMed  Google Scholar 

  33. Kistan J, et al. Pulmonary TB: varying radiological presentations in individuals with HIV in Soweto, South Africa. Trans R Soc Trop Med Hyg. 2017;111:132–6.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Greenberg SD, et al. Active pulmonary tuberculosis in patients with AIDS: spectrum of radiographic findings (including a normal appearance). Radiology. 1994;193:115–9.

    Article  CAS  PubMed  Google Scholar 

  35. Perlman DC, et al. Variation of chest radiographic patterns in pulmonary tuberculosis by degree of human immunodeficiency virus-related immunosuppression. Clin Infect Dis. 1997;25:242–6.

    Article  CAS  PubMed  Google Scholar 

  36. Pepper T, et al. Normal chest radiography in pulmonary tuberculosis: implications for obtaining respiratory specimen cultures. Int J Tuberc Lung Dis. 2008;12:397–403.

    CAS  PubMed  Google Scholar 

  37. Samb B, et al. Risk factors for negative sputum acid-fast bacilli smears in pulmonary tuberculosis: results from Dakar, Senegal, a city with low HIV seroprevalence. Int J Tuberc Lung Dis. 1999;3:330–6.

    CAS  PubMed  Google Scholar 

  38. Chaisson RE, et al. Tuberculosis in patients with the acquired immunodeficiency syndrome. Am Rev Respir Dis. 1987;136:570–4.

    Article  CAS  PubMed  Google Scholar 

  39. Jones BE, et al. Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. Am J Respir Crit Care Med. 1993;148:1292–7.

    CAS  Google Scholar 

  40. Hoyt KJ, et al. Effect of malnutrition on radiographic findings and mycobacterial burden in pulmonary tuberculosis. PLoS ONE. 2019;14:e0214011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mexitalia M, Dewi YO, Pramono A, Anam MS. Effect of tuberculosis treatment on leptin levels, weight gain, and percentage body fat in indonesian children. Korean J Pediatr. 2017;60:118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Diallo A, et al. Different profiles of body mass index variation among patients with multidrug-resistant tuberculosis: a retrospective cohort study. BMC Infect Dis. 2020;20:1–10.

    Article  Google Scholar 

  43. Murphy M, et al. Gender differences in tuberculosis treatment outcomes: a post hoc analysis of the REMoxTB study. BMC Med. 2018;16:1–11.

    Article  Google Scholar 

  44. LoMauro A, Aliverti A. Sex differences in respiratory function. Breathe. 2018;14:131–40.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


The authors would like to thank all the study participants for their participation and contribution to the study.


TGM was supported by the DST-NRF Centre of Excellence (CoE) in HIV Prevention (CoE UID number: 96354) and the Poliomyelitis Research Foundation (Grant no. 21/58). The funding sources listed here did not have any role in the analysis or preparation of the data in this manuscript, nor was any payment received by these or other funding sources for this manuscript. DA was supported through the SAMRC Self-Initiated Grant and the NRF of South Africa Thuthuka (grant no. TTK160517165310), the NRF Research Career Advancement Fellowship (grant no. RCA13101656388), the Poliomyelitis Research Foundation of South Africa (PRF 17/02) and an EDCTP fellowship (grant no. TMA2017SF-1960). AS was supported by EDCTP Career Development Fellowship (TMA2016CDF-1582). NP and the InDEX study is supported by EDCTP Senior Fellowship (grant no. TMA2018SF-2467).

Author information

Authors and Affiliations



Designed the study: AS, TGM;Performed the experiments: TGM, SN, SR, AS;Analysed the data: TGM, AS, ML;Wrote the first draft of the paper: TGM, AS;Collected specimens and clinical data: SC, KN; Supervised clinical and/or experimental aspects of the study: AS, NS, NP, KN, SC, RP, DA; All authors contributed to the editing and finalisation of the manuscript.

Corresponding author

Correspondence to Aida Sivro.

Ethics declarations

Ethics approval

The CAPRISA 020 Individualized M(X)drug-resistant TB Treatment Strategy Study (InDEX) was approved by the University of KwaZulu-Natal (UKZN) Biomedical Research Ethics Committee (BREC, BFC584/16) and registered with the South African Clinical Trials Register (NCT03237182). This sub-study was approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00002197/2020). All the experiments were performed in accordance with the Helsinki Declaration. All study participants provided written informed consent for the use of stored biological specimens.

Consent for publication

Not Applicable.

Competing interests

The authors declare no conflict of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Additional File 1: Supplementary Table 1 and Supplementary Figure 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maseko, T.G., Ngubane, S., Letsoalo, M. et al. Higher plasma interleukin − 6 levels are associated with lung cavitation in drug-resistant tuberculosis. BMC Immunol 24, 26 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: