Cure of murine candidiasis by recombinant soluble interleukin-4 receptor. receptor

Neutralization of interleukin (IL)-4 by specificantibody exerts therapeutic activity in a murine model of systemic candidiasis characterized by strong T helper type 2 (Th2) responses, To inves-tigate whether recombinant soluble IL-4 receptor (sIL-4R) could be used to block IL-4 action in vivo, mice treated with pharmacologic doses of sIL-4R at the time of infection were examined for progression of disease, development offootpad responses, serum IgE levels, and cytokine produc-tion in vitro by CD4+ lymphocytes. Following sIL-4R treatment, persistent ablation of circulat-ing IL-4 detected by ELISA was associated with a cure rate of>90 % in otherwise lethally infected mice, onset of durable protection, and a shift from a predominant Th2 to a Thl pattern ofreactivity. In addition, when administered to genetically susceptible adult mice with gastroin-testinal yeast colonization, the sIL-4R stimulated Thl-associated anticandidal resistance. Although the ability of Candida albicans to establish an infection relies on multiple virulence factors and handicaps to host defense, the ability of the fungus to persist in infected tissue or result in immunopathology may primarily involve down-regulation ofhost cell-mediated immunity [1-3]. Stud