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Neurology 1999;53:1409
© 1999 American Academy of Neurology
Articles

Shedding of TNF receptors in multiple sclerosis patients

Anna M. Jurewicz, MD, PhD, Agata K. Walczak, MD, PhD and Krzysztof W. Selmaj, MD, PhD

From the Laboratory of Neuroimmunology, Department of Neurology, Medical University of Lodz, Lodz, Poland.

Address correspondence and reprint requests to Dr. Krzysztof W. Selmaj, Department of Neurology, Medical University of Lodz, 22 Kopcinskiego str, 90-153 Lodz, Poland.

OBJECTIVE: To evaluate the rate of shedding of tumor necrosis factor (TNF) receptors (TNFRs) in MS patients.

BACKGROUND: It was previously suggested that TNF might play a significant role in the immunopathologic mechanism of MS. TNF mediates its biologic effects by interacting with two distinct receptors: TNFR-p55 and TNFR-p75. Both of these receptors exist in soluble and membrane-bound forms. Soluble receptors have been shown to influence TNF activity in vitro and in vivo and maintain balance between active, free TNF and inactive form of this cytokine bound to its soluble receptors.

METHODS: In the current study, the authors measured shedding of TNFRs from cell surface of peripheral blood mononuclear cells, peripheral blood lymphocytes, and monocytes in three groups of MS patients: relapsing–remitting in relapse, relapsing–remitting in remission, and chronic progressive.

RESULTS: The authors observed a significant distortion in generation of both soluble TNF receptors. Whereas the TNFR-p55 was shed at lower rate compared with healthy volunteers, the shedding of TNFR-p75 was significantly higher in MS patients.

CONCLUSION: Disturbance in TNFR shedding might contribute to the distortion of a fine balance between circulating TNF and its natural inhibitors in MS.

Key words: MS—Tumor necrosis factor—Peripheral blood mononuclear cells.




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