Elevated IP-10 and IL-6 from bronchoalveolar lavage cells are biomarkers of non-cavitary tuberculosis

Abstract

Background: Active TB disease can destroy lung parenchyma leading to cavities. Immune responses that predispose or protect individuals from lung damage during TB are poorly defined.

Objective: To sample lung immune cells and assay bronchoalveolar lavage (BAL) cell cytokine production.

Design: Enrolled subjects (n = 73) had bilateral infiltrates and underwent BAL.

Results: All had sputum culture demonstrating Mycobacterium tuberculosis and 22/73 (30%) had cavities on their chest radiograph. Those with cavities at presentation had a higher percentage of polymorphonuclear neutrophils (PMN) in BAL as well as lower inducible protein (IP) 10 (P < 0.01) and interleukin (IL) 6 (P = 0.013) in BAL cell supernatants compared to those without cavities. There was no correlation between cavities and other BAL or serum cytokines. IP-10 was negatively associated with BAL PMN. IP-10 and IL-6 expression above median reduces the odds of cavities by 79% and 78% in logistic regression models. IP-10 and IL-6 clustered with interferon-gamma and tumour necrosis factor-alpha in a principal component analysis, while IL-4 clustered with PMN.

Conclusion: Increasing IP-10 and IL-6 production by BAL cells is associated with non-cavitary TB in patients who present with radiographically advanced TB. IP-10 and IL-6 may reflect an effective T-helper 1 immune control pathway for TB, attenuating tuberculous lung destruction.

Figure 1. BAL cells cytokine elaboration in patients with an without cavities

Cavity status is shown on the X axis. Each cytokine measured in this investigation is shown by log transformed concentration on the Y axis. The median value is represented by the horizontal line. Only IL-6 and IP-10 showed significant differences with Mann–Whitney U test between patients with and without cavities, p value shown above the bracket.

Figure 2. Correlation of BAL supernatant IP-10 with BAL Polymorphonuclear Neutrophils (%)

Linear regressions with 95% confidence intervals. R² 0.071, p=0.026.

Figure 3. Principal Component Analysis

Component 1 explains 28.5% of variance and Component 2 18.1% variance. IFN-γ, IL-6, TNF-α, and IP-10 cluster together as a Th-1 response, and PMN, IL-4 and Total Cells/ml clustered as a Th-2 response. Cavities and IL-10 and IL-12p40 clustered together.