CURE OF MURINE CANDIDIASIS BY RECOMBINANT SOLUBLE INTERLEUKIN-4 RECEPTOR

Neutralization of interleukin (IL)-4 by specific antibody exerts therapeutic activity in a murine model of systemic candidiasis characterized by strong T helper type 2 (Th2) responses. To investigate 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 of footpad responses, serum IgE levels, and cytokine production in vitro by CD4(+) lymphocytes. Following sIL-4R treatment, persistent ablation of circulating 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 Th1 pattern of reactivity. In addition, when administered to genetically susceptible adult mice with gastrointestinal yeast colonization, the sIL-4R stimulated Th1-associated anticandidal resistance.