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Activation of the cytokine network in familial Mediterranean fever
N Gang1, J P Drenth, P Langevitz
1Heller Institute of Medical Research and Department of Medicine, Sheba Medical Center, Tel-Hashomer, Israel.
Objective:
To elucidate the role of cytokines in the pathogenesis of familial Mediterranean fever (FMF), an inherited disease characterized by attacks of serosal membrane inflammation.
Methods:
Blood samples were obtained from patients with FMF during attacks and remission. The cytokine concentrations in plasma and in supernatants from whole blood stimulated by bacterial lipopolysaccharide (LPS) were determined.
Results:
There were 27 patients with FMF, of whom 8 were studied during attacks, 9 during remission and 10 during both attack and remission. FMF attacks did not affect levels of plasma tumor necrosis factor-alpha (TNF-alpha) or interleukin 1beta (IL-1beta). In contrast, compared to remission, FMF attacks were associated with significantly higher mean levels of plasma IL-6 [8.4 pg/ml, 95% confidence interval (CI) 7.8-8.9 in remission vs 59 pg/ml, CI 21.4-96.7 during attacks; p=0.0005], sTNFr p55 (1.3 ng/ml, CI 1.2-1.4, vs 1.98 ng/ml, CI 1.6-2.3; p=0.005), and sTNFr p75 (2.9 ng/ml, CI 2.5-3.3, vs 4.09 ng/ml, CI 3.2-4.9; p=0.0249). The TNF-alpha, IL-1beta, and IL-6 content in supernatants derived from LPS stimulated blood cells was not modified by the attacks of FMF. Significant lower TNF-alpha release in LPS stimulated whole blood was detected in patients who were sampled in a later stage of the attacks (r=-0.54, p=0.047).
Conclusion:
Our results suggest that the cytokine network is activated during attacks of FMF. IL-6 appears to play an important role in the evolution of FMF attacks. Whether TNF-alpha or IL-1beta has a function in initiating the attacks remains to be established.
Insights
Familial Mediterranean Fever (FMF) attacks involve an activated cytokine network, with Interleukin-6 (IL-6) playing a key role in inflammation. Further research is needed to understand the role of Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-1beta (IL-1beta) in initiating FMF attacks.
Area of Science:
- Immunology
- Genetics
- Inflammation
Background:
- Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease.
- FMF is characterized by recurrent episodes of serosal membrane inflammation.
Purpose of the Study:
- To investigate the role of cytokines in the pathogenesis of FMF.
- To determine cytokine levels during FMF attacks and remission.
Main Methods:
- Blood samples collected from FMF patients during attacks and remission.
- Plasma and whole blood cytokine concentrations measured.
- Whole blood stimulated with lipopolysaccharide (LPS) to assess cytokine release.
Main Results:
- Interleukin-6 (IL-6) and soluble TNF receptors (sTNFr p55, sTNFr p75) were significantly elevated during FMF attacks compared to remission.
- Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-1beta (IL-1beta) plasma levels were not affected by FMF attacks.
- LPS-stimulated cytokine release from whole blood was not altered during attacks, though later-stage attacks showed reduced TNF-alpha release.
Conclusions:
- The cytokine network is activated during FMF attacks.
- IL-6 is implicated in the progression of FMF attacks.
- The role of TNF-alpha and IL-1beta in initiating FMF attacks requires further investigation.