Background The role of polymorphonuclear cells in the development of a chronic inflammatory process still remains controversial. Neutrophilic granules comprise various biologically active proteins, which play a pathogenic role in the development of chronic auto-immune diseases, such as rheumatoid arthritis. Elastase – a marker of primary granules, being a factor of protection in healthy individuals, may exert a pro-inflammatory effect in rheumatoid arthritis, promoting the degradation of the cartilage matrix and the activation of proteolytic enzymes. The constituent of secondary neutrophilic granules – lactoferrin – a 77 kDa protein with certain anti-microbal and anti-inflammatory properties.
Objectives To evaluate the role of constituents of neutrophilic granules ? lactoferrin and elastase ? in the pathogenesis of rheumatoid arthritis.
Methods In this study the serum levels of elastase and lactoferrin and an immunohistochemical staining reaction of polymorphonuclear cells for lactoferrin were assessed in 70 patients with rheumatoid arthritis.
Results The serum level of elastase – a marker of neutrophils’ activation – was dramatically increased in patients with rheumatoid arthritis in comparison to healthy persons (p < 0.001). However, the serum level of lactoferrin was significantly decreased in patients with rheumatoid arthritis (195.5 ± 11.7 ng/ml vs. 626.9 ± 20.8 ng/ml in healthy donors; p < 0.001). Blood neutrophils displayed weak staining for lactoferrin in rheumatoid arthritis. The decrease of serum level of lactoferrin and its concentration in polymorphonuclear cells was greater in patients who were diagnosed with extra-articular manifestations, such as rheumatoid nodules and Felty’s syndrome (p < 0.05). These patients also had greater serum level of elastase. The serum level of lactoferrin didn’t depend on the presence or absence of a rheumatoid factor or on the intensity of radiographic changes, but it inversely correlated with the serum levels of elastase, IgA, IgG, C-reactive protein and erythrocyte sedimentation rate. Treatment with non-steroidal anti-inflammatory drugs resulted in a clinical amelioration and was accompanied by the decrease of serum elastase level (p < 0.01). The serum level of lactoferrin was slightly raised after treatment (p < 0.05), which we consider to be a secondary effect due to decreased lactoferrin consumption. However, the intensity of neutrophilic staining reaction for lactoferrin remained unchanged.
Conclusion These data suggest a dysfunction of polymorphonuclear cells in rheumatoid arthritis: active synthesis and secretion of elastase is accompanied by the decreased synthesis of lactoferrin. The deficiency of lactoferrin – a potent antioxidant – may contribute to disease activity and the development of extra-articular manifestation in rheumatoid arthritis. The mechanism of this deficiency still remains unclear.
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