CURE OF MURINE CANDIDIASIS BY RECOMBINANT SOLUBLE INTERLEUKIN-4 RECEPTOR

Neutralization of interleukin (IL)-4 by specific antibody exerts thera peutic activity in a murine model of systemic candidiasis characterize d by strong T helper type 2 (Th2) responses. To investigate whether re combinant soluble IL-4 receptor (sIL-4R) could be used to block IL-4 a ction in vivo, mice treated with pharmacologic doses of sIL-4R at the time of infection were examined for progression of disease, developmen t of footpad responses, serum IgE levels, and cytokine production in v itro by CD4(+) lymphocytes. Following sIL-4R treatment, persistent abl ation of circulating IL-4 detected by ELISA was associated with a cure rate of >90% in otherwise lethally infected mice, onset of durable pr otection, and a shift from a predominant Th2 to a Th1 pattern of react ivity. In addition, when administered to genetically susceptible adult mice with gastrointestinal yeast colonization, the sIL-4R stimulated Th1-associated anticandidal resistance.