Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.
The properties and outcome of an immune response are best predicted by the lymphokine phenotype of the responding T cells. Cytokines produced by CD4+ T helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper T cell functions for antibody production. To determine whether induction of Th2-like cells would modulate an inflammatory response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease produced by Th1-like T cells specific for myelin basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease, the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition of the synthesis of inflammatory cytokines in the central nervous system (CNS). Modulation of an immune response from one dominated by excessive activity of Th1-like T cells to one dominated by the protective cytokines produced by Th2-like T cells may have applicability to the therapy of certain human autoimmune diseases.
Racke
M K
MK
Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Bonomo
A
A
Scott
D E
DE
Cannella
B
B
Levine
A
A
Raine
C S
CS
Shevach
E M
EM
Röcken
M
M
D000818:Animals; D001921:Brain / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006168:Guinea Pigs; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D016029:Receptors, Very Late Antigen / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D004676:Myelin Basic Protein; D016029:Receptors, Very Late Antigen; D015847:Interleukin-4; D007371:Interferon-gamma