IL-4 and IL-10 modulate autoimmune haemolytic anaemia in NZB mice.
New Zealand Black (NZB) mice spontaneously develop autoimmune haemolytic anaemia (AIHA). Here the effect of injecting NZB mice with plasmids encoding IL-4 (pIL-4) or IL-10 (pIL-10) on NZB disease was tested. Both constructs delayed the development of anaemia as judged by increased haematocrit values as compared with controls, but neither altered the IgG1 to IgG2 red blood cell (RBC) bound autoantibody levels. The increased haematocrit value was associated temporally with increased RBC bound IgG in NZB mice treated with pIL-10, but not pIL-4. By contrast, up-regulation of splenic macrophage FcgammaRIIb2 mRNA was associated temporally with increased haematocrit values in NZB mice given pIL-4. However, no such increase occurred in NZB mice that inhaled a peptide containing a dominant T-cell epitope, although this treatment is known to bias the autoimmune response towards Th2 and to reduce the severity of anaemia. It is considered that IL-4 treatment, in part, ameliorates NZB anaemia by increasing the expression of the inhibitory FcgammaRIIb2 and thereby reducing the capacity of splenic macrophages to phagocytose autoantibody coated RBC, but that this mechanism does not explain the beneficial effects of the inhaled peptide.
Youssef
A-R
AR
Department of Pathology and Microbiology, University of Bristol, Bristol, UK.
Shen
C-R
CR
Lin
C-L
CL
Barker
R N
RN
Elson
C J
CJ
D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology*; D000818:Animals; D004912:Erythrocytes / Q000276:immunology; D006400:Hematocrit; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D010957:Plasmids / Q000276:immunology; D012333:RNA, Messenger / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
C499172:Fcgr2b protein, mouse; D007074:Immunoglobulin G; D012333:RNA, Messenger; D017452:Receptors, IgG; D016753:Interleukin-10; D015847:Interleukin-4