Adding the immune‑boosting peptide thymosin‑alpha‑1 to the standard 6‑month TB drug regimen helped patients clear the infection faster, breathe better, and showed better immune and inflammation markers, without adding extra side effects.

<b>Aims/Background</b> Immunotherapy plays a critical role in the clinical treatment of tuberculosis, an infectious disease caused by <i>Mycobacterium tuberculosis</i>, in which immune damage promotes the occurrence and development of the disease. This study aimed to investigate the efficacy of thymosin &#x3b1;1 combined with the 2HRZE/4HR (2 months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by 4 months of isoniazid and rifampin) in the treatment of pulmonary tuberculosis and its effect on immune function and inflammatory factors. <b>Methods</b> A retrospective analysis was conducted on 106 pulmonary tuberculosis patients treated between October 2022 and June 2024. The patients were divided into two groups based on their treatment regimens: the control group (<i>n</i> = 47) received the 2HRZE/4HR treatment, while the observation group (<i>n</i> = 59) received thymosin &#x3b1;1 in addition to the 2HRZE/4HR treatment. All patients underwent a 6-month treatment course. Clinical efficacy was evaluated 6 months after treatment based on clinical symptoms and sputum smear results. The study compared foci resorption rates, cavity closure rates, and changes in pulmonary function indices, immune function indices, and inflammatory factor levels before and after treatment between the two groups. Adverse reactions were also recorded and analyzed. <b>Results</b> The total effective rate and the rate of foci resorption and cavity closure of the observation group were higher than the control group (<i>p</i> &lt; 0.05). After 6 months of treatment, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and peak expiratory flow (PEF) of the observation group were higher compared to the control group (<i>p</i> &lt; 0.05). Compared with the control group, the observation group exhibited lower mRNA expression of T-cell immunoglobulin mucin-1 (<i>TIM-1</i>) and <i>TIM-3</i>; reduced levels of immunoglobulin E (IgE), sputum supernatant, serum interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-&#x3b1;); but higher interferon-gamma (IFN-&#x3b3;) levels (<i>p</i> &lt; 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (<i>p</i> &gt; 0.05). <b>Conclusion</b> Thymosin &#x3b1;1 combined with the 2HRZE/4HR regimen holds promise as an effective treatment of pulmonary tuberculosis by improving immune function and pulmonary function of patients while attenuating the inflammatory response.