Emerging infectious diseases: a global problem.

1357-4310/00/$ see front matter © 2000 Elsevier Science Ltd. All rights reserved. Before treatment, the 13 patients were mounting a primarily T helper cell type 2 (Th2) immune response. This is typified by a surplus production of interleukin 10 (IL-10), an immunosuppressive cytokine, and a reduced production of g-interferon, a cytokine that activates other immune cells. After treatment, this pattern was reversed; IL-10 production fell, g-interferon production rose, and the pattern of the immune response returned to a more favourable Th1 response. IL-10 is known to inhibit the maturation of dendritic cells and natural killer (NK) cells and, during treatment, as IL-10 fell, there was a demonstrable burst of maturing dendritic cells and NK cells into the circulation. Frincke and colleagues suspect that the effect of HE2000 on dendritic cell maturation could hold the key to the mechanism of action of the drug, and perhaps to fundamental control mechanisms within the immune system itself. It may be that further research will uncover more about this control process but, in the next year or so, Frincke’s team aims to build on the results obtained in this preliminary trial and to concentrate on testing the efficacy of HE2000 more fully. HE2000 also shows promise in boosting immune response against other infectious diseases that result in a Th2 immune response – including malaria, hepatitis B and C and tuberculosis (TB). Future trials will investigate the efficacy of HE2000 against malaria; this infection does not have the long latency period of HIV/AIDS, and the trial will aim to establish the principle that the upregulation induced by HE2000 can actually fight infection. ‘Finding out whether the upregulation of the immune system that is elicited by HE2000 will prevent or improve the outcome of opportunistic infections is a critical next step,’ says Thomas Merigan, Hollis Eden Board member and Director of the Center for AIDS Research, Stanford University (Stanford, CA, USA). Another strong possibility for the future is combining HE2000 with an AIDS vaccine. ‘Much effort has gone into developing potential vaccines, but the problem is that a vaccine cannot effect an immune response in individuals whose immune system is suppressed.’ If this suppression could be reversed by HE2000, a combination therapy with a conserved epitope vaccine could be a realistic possibility for an effective therapeutic vaccine rather than a fleeting wisp of hope.