Effects of in vivo administration of interferon (IFN)-gamma, anti-IFN-gamma, or anti-interleukin-4 monoclonal antibodies in chronic autoimmune graft-versus-host disease.
These studies examined the role of cytokines in chronic autoimmune graft-versus-host disease (GVHD) in B6D2F1 mice injected with lymphoid cells from DBA/2 mice. Anti-interleukin (IL)-4 and anti-interferon (IFN)-gamma mAb, or IFN-gamma, were used in vivo to modulate B cell hyperactivity and disease. Kinetic experiments showed that, 2-3 weeks after induction, GVH mice had 100x elevated serum IgE, while IgG1 and IgG2a were 10x above normal. Early treatment with anti-IL-4 mAb or IFN-gamma decreased serum IgE and IgG1 and had no effect on IgG2a. Anti-IFN-gamma mAb treatment increased serum IgE and IgG1 while reducing IgG2a. This increase in serum immunoglobulins could be correlated with an increased spontaneous secretion of IL-4, IL-5, and IL-6 in spleen cell cultures from anti-IFN-gamma mAb-treated GVH mice. While neither anti-IFN-gamma nor IFN-gamma treatments altered the disease course, anti-IL-4 treatment delayed proteinuria and death in GVH mice. These observations suggest an important role for IL-4 in immune complex-mediated glomerulonephritis in chronic GVHD.
Umland
S P
SP
Schering-Plough Research, Bloomfield, New Jersey 07003.
Razac
S
S
Nahrebne
D K
DK
Seymour
B W
BW
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D002908:Chronic Disease; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007132:Immunoglobulin Isotypes; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology*; D015848:Interleukin-5 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D011507:Proteinuria; D013154:Spleen / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D015848:Interleukin-5; D015850:Interleukin-6; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma