INCREASED LEVELS OF SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR IN PATIENTS WITH MULTIPLE-SCLEROSIS AND HTLV-1-ASSOCIATED MYELOPATHY

Tumor necrosis factor-alpha (TNF-alpha) is a potent mediator produced by activated T lymphocytes and macrophages, which may play a role in t he pathogenesis and development of multiple sclerosis (MS) and HTLV-1- associated myelopathy (HAM). The first step in the induction of many b iological effects elicited by TNF-alpha is its binding to specific cel l surface receptors. A soluble form of TNF receptor (sTNF-R) can be de tected in the body fluid. We measured sTNF-R levels in the sera and ce rebrospinal fluid (CSF) of patients with either MS or HAM, and evaluat ed the correlation between this mediator and disease activity. The lev els of sTNF-R in the sera and CSF of patients with MS were significant ly increased compared with controls, particularly patients with acute relapsing MS during an exacerbation (P < 0.001). CSF levels of sTNF-R showed a strong correlation with those of TNF (r = 0.716, P < 0.001). Higher levers of sTNF-R in the sera of HAM patients were detected as c ompared with those of either controls (P < 0.001) or non-HAM carriers (P < 0.001). Patients with HAM exhibited significantly higher CSF leve ls of sTNF-R than those with other neurological diseases (P < 0.0001). These results suggest that the detection of sTNF-R in the sera and CS F may predict disease progression. Availability of such a marker would be useful in monitoring disease activity.