Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Goossens et al., 2020), and the lungs are the most common site of infection (Guo et al., 2022). Spinal tuberculosis is often secondary to pulmonary infection, with the thoracolumbar spine being the most commonly affected area (Kubihal et al., 2022; Na et al., 2023). Early symptoms of spinal tuberculosis are often subtle and nonspecific, including back pain, muscle spasms, and stiffness. As the disease progresses, the patient experiences worsening symptoms, including abnormal spine curvature, abscesses, and limited mobility. In addition, spinal tuberculosis can cause weakness, numbness, and paralysis of the legs by compressing and damaging nerves. “Early, Regular, Complete, Combined, Moderate” is the principle of TB treatment. For patients with stable, non-damaged vertebral bone, a cure can be achieved through treatment with anti-tuberculosis drugs alone. Surgery is necessary when medical treatment fails, there is significant bone destruction or spinal instability, or when there is compression of the spinal nerves. Preoperative anti-tuberculosis treatment and other adjuvant therapies are required to minimize the risk of surgery and recurrence of TB. However, there is currently no standardized presurgical anti-tuberculosis treatment specification, and the choice of surgical timing may require a precise treatment plan tailored to the individual patient’s condition.

In most cases of spinal tuberculosis, imaging reveals erosion and bone destruction of multiple neighboring vertebrae, which results in degenerative changes in the disc. Some cases may be characterized by swelling in the paravertebral or psoas major muscles, as well as abscess formation (Rajasekaran et al., 2018). Due to the severity of the disease, treatment for spinal tuberculosis typically lasts over 9 months (Garg and Goyal, 2020). Pathological diagnosis of spinal tuberculosis involves H&E staining, acid-fast staining, and molecular biology testing, which are considered the gold standard. The typical pathological changes caused by TB are characterized by chronic granulomatous inflammation accompanied by caseous necrosis. We conducted a preliminary comparison of the pathologic features of pulmonary and spinal tuberculosis. Our findings showed that the proportion of caseous necrosis, acute inflammation, abscess, exudation, and granulation tissue formation was significantly higher in the spinal tuberculosis group (Wu et al., 2023).

The immune response is crucial in preventing Mycobacterium tuberculosis infection. The process involves three pathological changes: exudation, proliferation, and degeneration/necrosis(Wang L et al., 2020). Macrophages, lymphocytes, neutrophils, and inflammatory factors secreted by them form tuberculosis granulomas that limit the spread of Mycobacterium tuberculosis and kill it (Ginsberg et al., 2016). After an early stage of inadequate control, Mycobacterium tuberculosis infection often reaches a state of equilibrium characterized by immune control and bacterial persistence (Chandra et al., 2022). It has been discovered that inflammation-associated cytokines play a crucial role in the progression of inflammation while Mycobacterium tuberculosis infects the host (Ma et al., 2019). Interleukin-10 (IL-10) plays a role in reducing the inflammatory response by interacting with other inflammatory factors, thereby impacting the progression of spinal tuberculosis (Liu et al., 2014). The high expression of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in spinal tuberculosis lesions was found to be associated with protective immune cells, and an imbalance in the expression of TNF-α, IFN-γ, and transforming growth factor-β (TGF-β) may exacerbate spinal tuberculosis hypersensitivity (Chen et al., 2014). In addition, macrophage migration inhibitory factor (MIF) has chemokine-like functions and plays a key role in a variety of acute and chronic inflammatory diseases (Wang et al., 2019). It has been reported that MIF may play an important role in the occurrence, development, and damage of spinal tuberculosis in the population of the northern province of China (Wang J et al., 2020).

Patient immunity may play a role in determining the length of anti-tuberculosis treatment and the timing of surgery for spinal tuberculosis. For this research, we gathered patients who suffered from spinal tuberculosis at different ages. We compared the differences in clinicopathologic features, immune cell subtypes and numbers, and expression of inflammation-associated factors. We aimed to provide important reference data for the clinical timing of surgery and the planning of postoperative treatment programs.

Patients with spinal tuberculosis often have comorbid pulmonary tuberculosis, with up to 67% of patients with spinal tuberculosis having a primary lung lesion or a history of tuberculosis reported (Mann et al., 2022). To ensure the accuracy of the study, we decided to exclude patients with pulmonary tuberculosis and those with a history of tuberculosis from our data collection. The study was limited to patients with simple spinal tuberculosis.

Spinal tuberculosis is the most common form of bone and joint tuberculosis, predominantly affecting the vertebrae. The tuberculosis bacterium can destroy the soft tissues between the vertebrae, causing them to fuse and narrowing the intervertebral space. Due to restricted blood flow, the vertebrae are susceptible to bone destruction, necrosis, caseous necrosis, and abscess formation. During the healing process, the body gradually absorbs part of the lesion products, which can lead to the proliferation of fibrous tissue and ultimately result in fibrous and bony healing. Early diagnosis, standardized treatment, and precise treatment significantly improve the prognosis of patients with spinal tuberculosis. Spinal tuberculosis surgery is usually preceded by two to four weeks of anti-tuberculosis treatment to keep the Mycobacterium tuberculosis in a quiescent phase. Our research revealed that the older group had a lower percentage of abscess formation compared to the younger and middle-aged groups before receiving anti-tuberculosis treatment. This could be attributed to a stronger immune response and increased infiltration of immune cells in younger patients. The unique structure of the spine makes it challenging to eliminate necrotic material that can cause abscess formation. Interestingly, the postoperative pathologic results showed a higher percentage of abscesses in the older group than in the younger and middle-aged groups, which contradicted the imaging findings. The reason for this phenomenon could be that the older group’s mild immune response might result in micro-abscesses that are challenging to detect through imaging. In addition, younger patients have stronger immunity and better preoperative anti-tuberculosis treatment, and abscesses are more easily cleared. Our findings offer guidelines for preoperative anti-tuberculosis treatment for spinal tuberculosis. For instance, extended preoperative anti-tuberculosis treatment may be appropriate for older patients. The WHO recommends that patients with tuberculosis of the bones or joints should receive nine months of treatment (Shanmuganathan et al., 2023). While 6 months of treatment is reportedly considered adequate, many experts still prefer 12-24 months of treatment (Garg and Somvanshi, 2011). On the other hand, it has been reported that surgical treatment is necessary for patients who have not responded to conservative treatment (with or without bracing or bed rest) after 3-4 weeks, due to pain or neurological deficits (Mak and Cheung, 2013). Persistent infection, progressive destruction of vertebral structures, or ensuing instability and deformity may cause pain. Imaging examination can be used to monitor the effectiveness of anti-tuberculosis treatment for uncertain cases.

Spinal tuberculosis is diagnosed through pathology and typically involves chronic inflammation with caseous necrosis. Our previous study found higher rates of caseous necrosis, acute inflammation, abscess, exudation, and granulation tissue formation in spinal tuberculosis compared to pulmonary tuberculosis (Wu et al., 2023). In this study, none of the pathologic features, except for abscesses, were statistically different between the groups. We examined the number and distribution of various immune cells in spinal tuberculosis lesions. The numbers of T cells, CD4⁺T cells, CD8⁺T cells, macrophages, lymphocytes, plasma cells, and NK cells were not statistically different between the three groups. CD4⁺ and CD8⁺ T cells were detected in HIV-negative spinal tuberculosis tissue sections, along with a population of CD68-positive macrophages in the tissue microenvironment (Danaviah et al., 2013). The number of CD20⁺ B cells was significantly higher in the younger group compared to the middle-aged and older groups. However, the clinical significance and value of this finding are unclear. B cells mediate humoral immune function and support the fight against TB. A decrease in B-cell immune response capacity may reduce the ability to clear Mycobacterium tuberculosis. While the function of immune cells in pulmonary tuberculosis has been widely studied, their role in tuberculous intervertebral disc tissue has been scarcely reported (Chen et al., 2022).

We compared the expression of inflammation-related factors and found significantly higher rates of positive TGF-β1 expression and high IL-10 expression in the older group compared to the younger group. TGF-β1 and IL-10 are important molecules that suppress the immune system. Research shows that increased expression of these molecules reduces the body’s defense against pathogens. TGF-β1 is a potent cytokine that significantly diminishes the biological function of macrophages (Yang et al., 2022), and also hinders the ability of TNF-α and IFN-γ to kill Mycobacterium tuberculosis (Hirsch et al., 1994). It has been suggested that TGF-β1 could potentially contribute to tissue damage and fibrosis in individuals suffering from TB (Kumar et al., 2016). Hyperactive TGF-β1 was detected in the lung lavage fluid and macrophages of patients with pulmonary tuberculosis (Aung et al., 2000; Bonecini-Almeida et al., 2004). Silencing the TGF-β1 gene along with first-line antituberculosis medications has been reported as a strategy to enhance the efficacy of antituberculosis drugs by promoting Mycobacterium tuberculosis clearance (Yang et al., 2022). IL-10 can combine with other inflammatory factors to suppress the body’s immune response, thereby triggering the occurrence and development of TB (Ma et al., 2019). An increase in IL-10 levels appears to aid Mycobacterium tuberculosis in surviving within the host body (Cavalcanti et al., 2012). It has been found that the combined production of the immunosuppressants IL-10 and TGF-β in patients with pulmonary tuberculosis may reduce host immunity against Mycobacterium tuberculosis, resulting in uncontrolled bacterial replication and causing overt disease (Bonecini-Almeida et al., 2004). Elevated levels of TGF-β1 and IL-10 in the tissues affected by spinal tuberculosis can lower the immune system’s ability to kill Mycobacterium tuberculosis. This could be one of the reasons why, after a period of anti-tuberculosis treatment, the proportion of abscesses is higher in older patients as compared to younger patients. IL-1β is a pro-inflammatory cytokine, and several studies have emphasized the importance of strictly regulating IL-1β during TB treatment (Silverio et al., 2021). Elevated levels of IL-1β are associated with tissue necrosis and cavity formation in TB patients (Tsao et al., 2000).

Structural and circulatory specificities result in different drug distribution in the spine for TB treatment. Drugs often fail to maintain effective concentrations in the sclerotic areas of the vertebral body and in the more closed tuberculous lesions, which leads to long-term recurrence in patients with spinal tuberculosis (Yang et al., 2022). Impaired immune function has been reported in elderly patients with pulmonary tuberculosis and the need to assess the immune status of patients to improve treatment outcomes (Liu et al., 2022). Based on our findings, monitoring IL-10 and TGF-β1 levels in older patients with spinal tuberculosis may be useful for evaluating the patient’s immune function and disease progression. It can also aid in making timely adjustments to drug therapy programs and deciding when surgical treatments are necessary.

The imaging examination before preoperative anti-tuberculosis therapy revealed a lower proportion of spinal tuberculosis abscesses in the older group, while the pathological examination of surgical specimens showed that the proportion of abscesses in the older group was higher than that in the younger and middle-aged groups. The high expression of IL-10 and TGF-β1 in the older group may have reduced their anti-tuberculosis immunity and treatment effectiveness. The timing of surgery and the duration of anti-tuberculosis treatment should vary in patients of different ages.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by the Ethical Committee of Chinese PLA General Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

SL: Writing – original draft, Writing – review & editing, Data curation, Formal Analysis, Investigation, Methodology, Resources, Software, Visualization. RW: Resources, Visualization, Writing – review & editing. MF: Investigation, Methodology, Writing – review & editing. HZ: Writing – review & editing. DL: Writing – review & editing. FW: Conceptualization, Writing – review & editing. WC: Conceptualization, Funding acquisition, Project administration, Writing – review & editing.