Smoking, inflammation and joint health: A toxicological perspective in knee osteoarthritis

The impact of smoking on osteoarthritis (OA) remains controversial. This study aimed to evaluate the effect of smoking, adjusted for body mass index (BMI) and medication use, on systemic and joint inflammation in patients with knee OA. Peripheral blood (PB), synovial fluid (SF), and histological samples were analyzed from patients stratified by smoking status, pain level (VAS), tobacco index (TI), and use of DMARDs, NSAIDs, and analgesics. IL-1β, IL-6, and TNF-α levels were measured by ELISA. Histological evaluation of extracellular matrix (ECM) used Alcian blue and Safranin O staining. Statistical analyses included ANOVA, Dunn's test, Spearman's and Kendall's correlations, and linear regression adjusted for age and BMI. RESULTS: Smoking OA patients (OA-S) showed significantly higher plasma TNF-α levels compared to non-smokers (OA-NS) (P<0.01), and reduced proteoglycan content (47.15%) compared to former smokers (OA-ExS) (72.74%) (P<0.01). A moderate negative correlation was observed between SF IL-1β and proteoglycans in OA-ExS. In OA-S, plasma TNF-α strongly correlated with SF IL-6 (P<0.05). Plasma TNF-α correlated with pain in OA-S, while IL-1β did so in OA-ExS (P<0.01). BMI positively correlated with SF IL-6 in OA-S (P<0.01). Analgesic and NSAID use were associated with increased plasma TNF-α in OA-S and OA-ExS. Regression models showed that smoking was significantly associated with elevated plasma TNF-α and SF IL-6 levels, independent of BMI and age. CONCLUSION: Smoking, combined with excess weight and medication use, may enhance chronic inflammation and contribute to increased severity of knee OA.