TRANSIENT INCREASE IN SYMPTOMS ASSOCIATED WITH CYTOKINE RELEASE IN PATIENTS WITH MULTIPLE-SCLEROSIS

Fourteen patients with multiple sclerosis were treated with the humani zed monoclonal antibody CAMPATH-1H which targets the CD52 antigen pres ent on all lymphocytes and some monocytes; four also received anti-CD4 antibody. Lymphopaenia developed rapidly and was sustained for at lea st 1 year. In 12 patients, the first infusion of antibody was characte rized by significant exacerbation or re-awakening of pre-existing symp toms lasting several hours. These clinical effects of antibody treatme nt correlated with increased levels of circulating cytokines. Peak lev els of tumour npcrosisfactor (TNF)-alpha and interferon (IFN)-gamma oc curred at 2 h, whereas the rise in interleukin-6 (IL-6) was significan tly delayed and peaked at 4 h after starting antibody treatment. There was a decline in CH50, indicating complement activation. The neurolog ical symptoms could not be attributed directly to pyrexia and were not provoked (in one patient) by an artificial rise in temperature. In th e remaining two patients, a single pre-treatment with intravenous meth ylprednisolone (500 mg) prevented both the transient increase in neuro logical symptoms and the cytokine release, Our results, involving 14 i ntensively studied patients treated with humanized monoclonal antibodi es, suggest that soluble immune mediators contribute to symptom produc tion in multiple sclerosis; the mechanism remains uncertain but, on th e available evidence, we favour the interpretation that cytokines dire ctly affect conduction through partially demyelinated pathways.