The serum level of hepcidin that increases with inflammation and decreases with hypoxia and anemia brings into mind that COPD can be controlled by a complex alarm network. Hepcidin is a liver-produced peptide implicated in the anemia of inflammation.[10
] Inflammation increases hepcidin expression. Also, serum hepcidin was abnormally increased in patients with inflammation (CRP>10 mg/l), in patients with multiple myeloma[12
] and in patients with chronic kidney disease[14
] without associated inflammatory disorders. In a study, it was found that hepcidin was expressed by airway epithelial cells and was induced by both interferon gamma and IL-6 in a cell-specific pattern andmay serve as a protective factor through its direct antimicrobial effects.[15
In another study it was shown that hepcidin is also produced in mouse macrophages infected with intracellular Mycobacteria.[16
] However, there are conflicting findings about serum hepcidin level related to acute and chronic inflammation in the literature. In a previous study, the pro-hepcidin concentration was significantly higher in the patients with active rheumatoid artritis (RA) than those with inactive to moderate RA.[17
On the other hand, in another study, it is reported that RA patients have higher serum concentration of pro-hepcidin than patients with systemic lupus erythematosus and healthy volunteers, but the pro-hepcidin concentration does not correlate with RA disease activity scores, tumor necrosis factor-alpha
(TNF-α), or IL-6.[18
] All of our patient groups were in stabilface of the COPD. Our patient groups and control group had no anemia and high serum CRP levels. Hepcidin plays a crucial role in the anemia of chronic disease. We think that in our severe COPD patient group, the decrease in serum hepcidin levels is related to hypoxemia rather than inflammation. In our study, serum hepcidin levels were significantly different between the healthy control group and the moderate COPD patient group (P
=0.004), between healthy control group and severe (P
=0.002) COPD patient group, between the mild and moderate COPD (P
=0.001) patient groups, and between the mild and severe COPD (P
=0.003) patient groups. These findings suggest that hepcidin could be an important marker which could be used to evaluate the disease state. In COPD patients, tissue hypoxia occurs when the partial oxygen pressure (Pa02) falls below 60 mmHg which causes systemic effects. Serious complications may occur when vital organs cannot receive sufficient oxygen. Hypoxemia is seen more in the severe COPD patient group than in the mild and moderate COPD patient groups. Systemic hypoxia reduced hepcidin production in the liver. However, the molecular mechanisms in which hypoxemia plays a role to repress hepcidin production has not yet been fully understood.[19
] In our severe COPD patient group, there was positive correlation between serum hepcidin levels and Pa02 (P
=0.000). This result demonstrates that there is a correlation between the degree of hypoxemia and the serum hepcidin level in the severe COPD patient group.
Along with the age, a decrease in lung and chest wall compliance, an increase in prevalence of a ventilation-perfusion disorder, low arterial oxygen pressure, and an increase in physical dead space make hypoxemia more apparent. In our study, in the severe COPD patient group, serum hepcidin levels decreased with aging (P=0.003). However, this relation may come from multifactorial reasons and more likely to be related to hepatic function.
The hepatic synthesis of hepcidin increases when serum iron concentration goes up. In contrast, hepcidin synthesis decreases when there is iron deficiency. Our results showed that the serum hepcidin level increased with increasing hct (P=0.009) and serum iron (P=0.000) levels in the severe COPD patient group. Hepcidin production also correlated with the serum ferritin level. It was found that the serum hepcidin level increased when the serum ferritin level increased (P=0.012) in the severe COPD patient group.
Further studies are needed to clarify this issue and the role of inflammatory and iron regulatory pathways in hepcidin synthesis in COPD patients.
BMI has a negative effect on the quality of life of patients with COPD, and previous studies have found a relationship between poor prognosis, mortality, and BMI.[20
] In one study, no relationship was found between TNF-α, interferon-γ (IFN-γ) and hepcidin.[9
] A number of studies have found a relationship between low BMI and TNF-α.[22
] Also, The correlation between serum hepcidin levels and BMI was shown in some studies on obesity.[24
] All of our patients had normal or low BMI. In our study, no relationship was found between BMI and serum hepcidin levels in the moderate and severe COPD patient groups. Only a positive correlation was found between hepcidin levels and BMI (P
=0.01) in mild COPD patient group.
Impaired pulmonary function is a strong risk factor for the development of COPD and a marker of disease severity. In our study, no relationship between respiratory function parameters and hepcidin in the mild and moderate COPD patient groups was found, whereas there was an increase in the hepcidin level (P=0.006) with the increase in the FEV1/FVC level in the severe COPD patient group.
Limitation of the study
The limitation of the study is that many of the patients admitted to our clinic for COPD were either in an inflammation stage or had additional diseases. Therefore, we think that more studies using a larger number of patients need to be done.