Background <p>This study explores correlations between serum IL-6 levels, lipid metabolism, and nutritional status in pulmonary tuberculosis patients to advocate for integrating metabolic-nutritional assessments into routine TB care. It addresses a critical gap in current guidelines by linking IL-6-mediated inflammation to metabolic health, aligning with WHO’s holistic care principles.</p> Methods <p>A case-control study was employed, which included 724 hospitalized patients diagnosed with pulmonary tuberculosis (the case group) from the tuberculosis department of a tertiary hospital between January 2023 and December 2023, matched with 724 healthy individuals who served as the control group. The indicators measured included lipid profile [Triglycerides (TG), Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C) and Low-Density Lipoprotein Cholesterol (LDL-C)], nutritional indicators [Total Protein (TP), Albumin (ALB) and Globulin (GLB)], and inflammatory indicators (IL-6). Statistical analyses employed SPSS 18.0, utilizing the Mann-Whitney U test for intergroup comparisons and Spearman’s correlation for association analyses, and multiple linear regression to identify independent predictors of serum IL-6 levels.</p> Results <p>Compared to the control group, the case group had significantly lower levels of TG, TC, HDL-C, LDL-C, TP, and ALB (<i>Z=-25.107~-3.619, all P = 0.000), while GLB levels were significantly elevated (Z=-7.113, P = 0.000</i>). After adjusting for 5 confounders, Spearman’s partial rank correlation analysis showed that TP had a positive correlation with TC, HDL-C and LDL-C (<i>r = 0.115 ~ 0.181, P = 0.000 ~ 0.002</i>), ALB had a positive correlation with TC and HDL-C (<i>r = 0.271 ~ 0.466; all P = 0.000</i>), while GLB had a negative correlation with HDL-C and LDL-C (<i>r = -0.096~-0.266, P = 0.000 ~ 0.010</i>). IL-6 was negatively correlated with TC, TG, HDL-C and LDL-C (<i>r = -0.971~-0.220, all P = 0.000</i>), and negatively correlated with TP and ALB (<i>r = -0.253~-0.163, all P = 0.000</i>). Multiple linear regression analysis, after controlling for confounders and addressing multicollinearity, further identified lower levels of LDL-C, HDL-C, triglycerides (TG), and globulin (GLB) as significant independent predictors of higher serum IL-6 concentrations (all P &lt; 0.05). The final model explained a substantial proportion of the variance in IL-6 levels (Adjusted R² = 0.913).</p> Conclusion <p>This study reveals that patients with pulmonary tuberculosis exhibit a metabolic-nutritional phenotype characterized by “hypolipidemia, hypoalbuminemia, and hyperglobulinemia”. Beyond correlation, multiple linear regression identified specific lipid fractions (LDL-C, HDL-C, TG) and globulin as independent predictors of IL-6 levels, indicating that IL-6 levels are significantly associated with these abnormalities and may reflect a shared underlying dysregulatory pathway. This research reinforces the management concept of viewing tuberculosis as a systemic metabolic disease and highly recommends that clinicians incorporate assessments of specific lipid profiles and protein fractions as a routine component of comprehensive tuberculosis management, with the goal of breaking the vicious cycle of “tuberculosis, malnutrition, and decreased immunity.” This approach could ultimately lead to better treatment outcomes for tuberculosis worldwide.</p> Clinical trial number <p>Not applicable.</p>