# Interleukin-6 signaling, lung injury, and post-TB lung disease in TB-HIV

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $743,698

## Abstract

ABSTRACT
Tuberculosis (TB) is among the leading infectious killers worldwide with over 10 million new cases and 1.5 million
deaths each year. Pulmonary TB, the most common form of the disease, is associated with lung injury that can
persist beyond treatment completion. Post-TB lung disease (PTLD) is an important contributor to excess
disability and mortality that can affect an estimated 155 million TB survivors globally. Yet there are no known
interventions to prevent TB-associated lung injury and the likelihood of subsequent PTLD. The goal of this R01
proposal is to characterize the burden, severity, and phenotypic presentation of PTLD, and its association with
interleukin-6 (IL-6) signaling pathways, in TB patients with and without HIV. We will leverage the ongoing NIH
and Indian Government funded RePORT-India TB Research Consortium, a multi-site study that is prospectively
evaluating HIV-uninfected adults with drug-sensitive TB for lung injury during and after TB treatment, by enrolling
a comparison cohort of HIV-positive drug-sensitive TB patients matched on age, sex, and smoking exposure
who will follow identical study protocols. Through Aim-1, we will extensively characterize and compare the
phenotypic differences in lung injury at TB treatment initiation, its resolution during treatment, and subsequent
PTLD between TB patients with versus without HIV using a multi-dimensional approach of pulmonary function
testing, respiratory health and functional status assessments, and novel lung imaging approaches. Through Aim-
2, we will use induced sputum samples to comprehensively investigate the role of different IL-6 signaling
pathways in determining the extent of lung injury, and its resolution during TB treatment, by measuring key
immune, cellular, and gene expression markers, along with downstream inflammatory pathways linked to acute
lung injury and fibrotic remodeling. This R01 application will expand upon our prior and ongoing research in India
and generate evidence to support the design of clinical trials of host-directed therapies for selectively modulating
IL-6 signaling pathways to improve pulmonary outcomes in TB patients with and without HIV.

## Key facts

- **NIH application ID:** 10924557
- **Project number:** 1R01AI184179-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Devasahayam Jesudas Christopher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $743,698
- **Award type:** 1
- **Project period:** 2024-09-20 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924557

## Citation

> US National Institutes of Health, RePORTER application 10924557, Interleukin-6 signaling, lung injury, and post-TB lung disease in TB-HIV (1R01AI184179-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10924557. Licensed CC0.

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