Antigen-specific suppression of inflammatory arthritis using liposomes.
Existing therapies for rheumatoid arthritis and other autoimmune diseases are not Ag specific, which increases the likelihood of systemic toxicity. We show that egg phosphatidylcholine liposomes loaded with Ag (OVA or methylated BSA) and a lipophilic NF-kappaB inhibitor (curcumin, quercetin, or Bay11-7082) suppress preexisting immune responses in an Ag-specific manner. We injected loaded liposomes into mice primed with Ag or into mice suffering from Ag-induced inflammatory arthritis. The liposomes targeted APCs in situ, suppressing the cells' responsiveness to NF-kappaB and inducing Ag-specific FoxP3(+) regulatory T cells. This regulatory mechanism suppressed effector T cell responses and the clinical signs of full-blown Ag-induced arthritis. Thus, liposomes encapsulate Ags and NF-kappaB inhibitors stably and efficiently and could be readily adapted to deliver Ags and inhibitors for Ag-specific suppression of other autoimmune and allergic diseases.
Capini
Christelle
C
Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
Jaturanpinyo
Montree
M
Chang
Hsin-I
HI
Mutalik
Srinivas
S
McNally
Alice
A
Street
Shayna
S
Steptoe
Raymond
R
O'Sullivan
Brendan
B
Davies
Nigel
N
Thomas
Ranjeny
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D003474:Curcumin / Q000008:administration & dosage; D004337:Drug Carriers / Q000008:administration & dosage / Q000627:therapeutic use; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008081:Liposomes / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000008:administration & dosage; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D011794:Quercetin / Q000008:administration & dosage; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D013450:Sulfones / Q000008:administration & dosage
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D000939:Epitopes; D007166:Immunosuppressive Agents; D008081:Liposomes; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D012710:Serum Albumin, Bovine; D010047:Ovalbumin; D011794:Quercetin; D003474:Curcumin