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Increased TNF-alpha secretion by alveolar macrophages from patients with rheumatoid arthritis
P Gosset1, T Perez, P Lassalle
1Centre d'Immunologie et de Biologie Parasitaire, Unité mixte INSERM, CNRS, Lille, France.
Abstract:
Tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) production by alveolar macrophages (AM) was evaluated in 17 rheumatoid arthritis (RA) patients without interstitial lung disease (ILD, Group 1) and 14 RA patients with clinical ILD (Group 2) in comparison with 10 control subjects. AM after recovery by bronchoalveolar lavage were selected by adherence, and then supernatants were collected after 3 or 24 h of culture. Results showed no modification of IL-1 synthesis in either group of RA patients. Spontaneous TNF production was significantly increased in Group 2 (2.5 +/- 0.5 ng/ml) as well as in Group 1 (2.4 +/- 0.4 ng/ml) compared with control subjects (0.43 +/- 0.1 ng/ml, p less than 0.001). In addition, AM from patients untreated or treated exclusively by nonsteroidal antiinflammatory drugs produced similar levels of TNF, whereas those receiving corticosteroids, second-line drugs (such as sulfasalazine, aurothiomalate, and methotrexate), or the combination of both therapy regimens released significantly less TNF. Interestingly, TNF was not different in both groups, but Group 2 had a markedly increased ratio of local immune complex to albumin in bronchoalveolar lavage fluid (0.47 +/- 0.12 versus 0.07 +/- 0.02 in Group 1; p less than 0.002). TNF thus appears an additional component of RA subclinical alveolitis in RA, but its prognostic value and its precise role in lung damage remain to be determined. Development of ILD requires certainly complex interactions of synergistic factors, possibly including local immune complexes detected in BAL fluids.
Insights
Tumor necrosis factor alpha (TNF) is elevated in rheumatoid arthritis (RA) patients with and without lung disease. This suggests TNF may play a role in RA-related lung inflammation, but its exact function requires further study.
Area of Science:
- Immunology
- Rheumatology
- Pulmonology
Background:
- Rheumatoid arthritis (RA) can affect the lungs, leading to interstitial lung disease (ILD).
- Alveolar macrophages (AM) play a role in RA pathogenesis and lung inflammation.
- Tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) are key inflammatory cytokines implicated in RA.
Purpose of the Study:
- To investigate TNF and IL-1 production by AM in RA patients with and without ILD.
- To compare cytokine levels in RA patients to healthy controls.
- To explore the relationship between TNF production, ILD, and treatment in RA.
Main Methods:
- Bronchoalveolar lavage (BAL) was performed on RA patients (with and without ILD) and controls.
- Alveolar macrophages (AM) were isolated and cultured.
- TNF and IL-1 levels in cell culture supernatants were measured using ELISAs.
Main Results:
- Spontaneous TNF production was significantly higher in RA patients (Groups 1 and 2) compared to controls.
- IL-1 synthesis was not significantly different across the groups.
- Patients treated with corticosteroids or second-line RA therapies showed reduced TNF production.
- RA patients with ILD had a higher ratio of local immune complexes to albumin in BAL fluid.
Conclusions:
- Elevated TNF production by AM is a feature of RA, even in the absence of clinical ILD.
- TNF may be an important factor in the subclinical lung inflammation associated with RA.
- The development of ILD in RA likely involves complex interactions, potentially including local immune complexes in BAL fluid.