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.
Puccetti
P
P
Department of Experimental Medicine, University of Perugia, Italy.
Mencacci
A
A
Cenci
E
E
Spaccapelo
R
R
Mosci
P
P
Enssle
K H
KH
Romani
L
L
Bistoni
F
F
D000818:Animals; D002177:Candidiasis / Q000276:immunology / Q000628:therapy*; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009061:Mouth Mucosa / Q000382:microbiology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins / Q000627:therapeutic use; D012995:Solubility; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E