Twenty-one patients with tropical spastic paraparesis (TSP), all of whom were born in the Caribbean and who had migrated to the United Kingdom, are described. All had a progressive spastic paraparesis developing many years after immigration and all 19 tested had antibodies to the human T cell lymphotropic retrovirus type 1 (HTLV1). The clinical and laboratory features and visual, auditory and somatosensory evoked potentials are described. Details of magnetic resonance scanning of the brain and, in a few cases, the spinal cord are compared with those found in multiple sclerosis. The antibody titres to HTLV1 assessed by particle agglutination, Western blot, antibody-directed cell mediated cytotoxicity and pseudotype neutralization were higher than in asymptomatic infected relatives and in patients with adult T cell leukaemia. Some, but not all, of the IgG oligoclonal bands in the CSF were directed against HTLV1. IgM oligoclonal bands directed against HTLV1 were found in 2 patients. Sixty of the 64 first degree relatives of 11 Jamaican patients with TSP were traced in the UK and the Caribbean; 20-30% of those born in the Caribbean had antibodies to HTLV1, irrespective of their present place of residence, whilst none of those born in the UK, who were the children of the patients, had antibodies. The original pathological material obtained from the Caribbean by Montgomery et al. (1964) is reviewed. These results are discussed in relation to animal retroviral neurological diseases, particularly visna in sheep which has clinical and pathological features closely similar to TSP. It is proposed that TSP is due to a HTLV1 infected lymphocyte/macrophage immune-mediated inflammatory response in the spinal cord.

T lymphocytes may play a central role in MS. The search for more targeted immunosuppression than is currently available has led to recent clinical trials of novel therapeutics. We studied 29 patients in a double-blind placebo-controlled trial of the chimeric monoclonal anti-CD4 antibody, cM-T412 (Centocor, Leiden, Holland) over a period of 18 months. Total and differential WBC counts; T, B, and natural killer lymphocytes; CD4+ and CD8+ T cells; CD4+ and CD4- naive cells; CD4+ and CD4- memory cells; interleukin-2 receptor- and major histocompatibility class II-positive T cells; serum tumor necrosis factor alpha (TNF-alpha); and PHA (phytohemagglutinin)/LPS (lipopolysaccharide)-stimulated whole blood TNF-alpha production were all examined serially in peripheral blood for the duration of the trial. In addition, for the first two treatment cycles, the above variables were tested 1 and 7 days after treatment. The results demonstrated significant long-term reductions, lasting up to 12 months after the last treatment cycle in all CD4+ subsets studied, but with a relative preservation of CD4+ memory cells as opposed to CD4+ naive cells. CD4- subsets also showed significant reductions after treatment but returned to baseline levels within 7 days. Monocyte counts were unaffected by cM-T412. Serum TNF-alpha and 2- and 18-hour PHA/LPS-stimulated TNF-alpha levels were also unchanged in the long term, although significant increases were observed in the 2- and 18-hour PHA/LPS-stimulated TNF-alpha levels the day immediately after treatment. There was no significant correlation between any of the immunologic markers studied and MRI measures of disease activity.

Certain elderly humans show a blunted fever response to infection. A study was designed using a murine model to assess the influence of age on the febrile response to the endogenous pyrogen, tumor necrosis factor alpha (TNF alpha). Twenty (10 young: 4-6 months; 10 old: 24-28 months) BALB/c mice were injected with 50 ng of TNF alpha into the intraperitoneal space; the experiments were repeated one week later with 100 ng TNF alpha. Control animals received intraperitoneal injections of pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 90 minutes post-injection using a thermistor probe and temperature gauge. In the majority of the time intervals following injection, the mean temperature changes of young mice were significantly higher than old mice for both 50 ng and 100 ng doses of TNF alpha. Similarly, peak temperature changes from baseline were consistently higher in young animals following injection of TNF alpha. Moreover, the peak temperature changes in young mice after 50 ng TNF alpha injection were significantly higher than those in old mice following a 100 ng injection of TNF alpha. These findings confirm that (a) TNF alpha has a role in the pathogenesis of fever; (b) aging alters significantly the febrile response; and (c) a mechanism of this age-related blunted febrile response may involve TNF alpha.