Features of cytokine regulation of fibrotic reactions in patients with co-morbid chronic pancreatitis and chronic obstructive pulmonary disease

In chronic pancreatitis (CP), oxidative stress, imbalances in growth factors and cytokines activate pancreatic stellate cells. The activity level of TGF‑β determines the intensity of pancreatic fibrosis. In comorbid cases of CP and chronic obstructive pulmonary disease (COPD), a state of chronic systemic inflammation develops. This is associated with increased tumour necrosis factor α (TNF‑α), interleukin‑6, and TGF‑β levels in the systemic circulation, promoting fibrogenesis progression in both the pancreas and lungs. Objective — to determine the role of pro‑inflammatory cytokine production in the development and progression of CP in patients with COPD. Materials and methods. A total of 180 patients aged between 45 and 60 years were examined: 60 with CP, 60 with CP and COPD, and 60 with COPD. A control group was formed comprising 20 practically healthy individuals (PHI) aged between 47 and 60 years. Results. Compared to practically healthy individuals (PHI), patients with CP and COPD exhibited a greater degree of immune‑inflammatory activation. This was evidenced by increased levels of TGF‑β1 (by 6.2 times), TNF‑α (by 5.2  imes), and IL‑1β (by 7.4 times) (all p<0.05). This inflammatory activity was more pronounced in patients with COPD alone, where levels of TGF‑β1, TNF‑α, and IL‑1 increased by 5.2, 4.3, and 5.5 times respectively, compared to 3.5, 3.3, and 3.8 times increases in CP patients (all p<0.05). Serum insulin‑like growth factor 1 (IGF‑1) levels exceeded reference values by 2.1 times in CP patients (p<0.05) and by 3.1 times in those with comorbid CP and COPD (p<0.05), while COPD patients exhibited only 1.5 times increase (p<0.05). C‑reactive protein (CRP) levels were also significantly elevated in CP patients (by 13.3 times). In those with comorbid CP and COPD, CRP levels surged by 21.5 times (p<0.05), indicating a higher degree of inflammation in cases of comorbidity. Differences in pancreatic exocrine insufficiency (PEI) severity were noted across groups. The total symptom score (TSS), calculated using the Pancreatic Exocrine Insufficiency Questionnaire (РЕІQ) questionnaire, was by 7.3 times higher than PHI values in isolated CP cases (p<0.05). In comorbid CP‑COPD scenarios, the TSS rose by 9.2 times (p<0.05), indicating a high level of exocrine pancreatic insufficiency. Fecal elastase‑1 levels dropped by 1.9 times in CP patients (p<0.05). However, in comorbid cases, elastase‑1 deficiency was more pronounced, decreasing by 4.5 times (p<0.05). Conclusions. Patients with CP and comorbid COPD show hyperproduction of growth factors (TGF‑β1, IGF) and pro‑inflammatory cytokines (TNF‑α, IL‑1β). The systemic inflammatory process driven by these cytokines and growth factors contributes to pancreatic tissue damage, inflammation, hyperenzymemia, progressive exocrine insufficiency, and activation of fibrotic reactions in the pancreas and lungs. A strong direct correlation was observed between TNF‑α levels in blood and α‑amylase, CRP, and TSS values, as well as a moderate inverse correlation between TGF‑β1, IL‑1β, and elastase‑1 levels in faeces. There was also a weak inverse correlation between IGF‑I, TGF‑β1, and fecal elastase‑1 levels.