Suramin treatment suppresses induction of experimental autoimmune uveoretinitis (EAU) in rodents.
The experimental drug suramin has been shown to possess several immunosuppressive properties. In this study we investigated the effect of suramin on the development of experimental autoimmune uveoretinitis (EAU) in mice and in rats. EAU was induced either by active immunization with a uveitogenic protein or peptide, or by the adoptive transfer of a uveitogenic T cell line. The development of EAU was assessed by clinical evaluation as well as by histopathology. Immunological responses were measured by delayed type hypersensitivity (DTH), lymphocyte proliferation, and serum antibody levels to the immunizing antigen. Suramin treatment was most effective in suppressing EAU when started concurrently with immunization (afferent). Treatment was less effective in suppressing disease when first administered 7 days after immunization or when given to animals that received an adoptive transfer of uveitogenic T cells (efferent). The effect of suramin on DTH and lymphocyte proliferation roughly paralleled its effect on EAU. Aferent treatment of mice with suramin completely suppressed anti-IRBP antibody titers. Interestingly, animals receiving efferent treatment had unreduced IgM levels but little or no IgG, suggesting prevention of the IgM-to-IgG switch. Depressed in vitro lymphocyte proliferative responses in animals treated with suramin during the afferent stage suggested that the suppressive effect on disease was due at least in part to an inhibition of antigen priming. Our results suggest that suramin merits further investigation as a potential treatment for some types of uveitis.
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA.
G
G
Sartani
P B
PB
Silver
G
G
Strassmann
C C
CC
Chan
R R
RR
Caspi
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010455:Peptides; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins / Q000276:immunology; D013498:Suramin / Q000627:therapeutic use*; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D010455:Peptides; D012177:Retinol-Binding Proteins; D013498:Suramin; D000099214:Retinol-Binding Proteins, Interstitial