THE ROLE OF CYTOKINES IN TOXOPLASMOSIS

Infection with Toxoplasma gondii is normally asymptomatic, but as a co nsequence of the AIDS epidemic the incidence of symptomatic disease an d especially toxoplasmic encephalitis (TE) has grown in frequency. The high frequency of adverse reactions to conventional therapeutic regim ens for toxoplasmosis highlight the need to develop new strategies for the management of this disease. The importance of cytokines in resist ance against T. gondii has been shown primarily in murine models of to xoplasmosis and a number of cytokines (e.g., IFN-gamma, TNF-alpha, IL- 2 and IL-12) have been proposed for trials in patients with TE. One me chanism by which these cytokines produce their effects is through stim ulation of macrophages and/or NK cells. However, there are problems wi th immunological intervention in immunocompromised patients with TE si nce the infection is present primarily in the central nervous system ( CNS), an immunoprivileged site, and because certain cytokines may down regulate the immune response. While much valuable information has bee n obtained from studies conducted in immunocompetent strains of mice t heir relevance to an immunocompromised host is unknown. The developmen t of genetically altered mice with immune deficiencies offers promisin g new models that may allow for more rational development of new treat ment regimens.