Protective major histocompatibility complex genes and the role of interleukin-4 in collagen-induced arthritis.
To investigate the role of interleukin (IL)-4 during the triggering of collagen-induced arthritis, we examined the effects of the I-A(b) and I-E protective/suppressive genes and passively administered anti-IL-4 monoclonal antibody. In contrast to the action of I-E expression on its own, which has mainly a suppressive effect post-triggering, the combination of I-A(b) and I-E had a marked protective effect. Assuming, on the basis of previous experience with the I-A(b) allele, that it might act through suppressing early IL-4 production, we treated mice with the 11B11 IL-4-neutralizing antibody around the time of initial immunization with collagen. Treatment over a period extending to 6 days post-immunization exacerbated the arthritis, but when curtailed to 2 days post-immunization (and tested in pristane-primed animals), the disease was reduced. We conclude that IL-4 plays an essential role in triggering the disease.
Hesse
M
M
Deutsches Rheuma-Forschungs-Zentrum, Berlin, Germany.
Bayrak
S
S
Mitchison
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D003094:Collagen; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D015847:Interleukin-4; D003094:Collagen