Folate-targeted immunotherapy effectively treats established adjuvant and collagen-induced arthritis.
Activated macrophages express a cell surface receptor for the vitamin folic acid. Because this receptor is inaccessible or not measurably expressed on other normal cells, folic acid has been recently exploited to selectively deliver attached radio-emitters to sites of activated macrophage accumulation, allowing scintigraphic imaging of inflamed joints and organs of arthritic rats. We demonstrate here that folate-linked haptens can also be targeted to activated macrophages, decorating their cell surfaces with highly immunogenic molecules. Under conditions in which the rodent has already been immunized against keyhole limpet hemocyanine-(fluorescein isothiocyanate) FITC, activated macrophages are eliminated. Administration of folate-FITC conjugates to rodents with experimental arthritis attenuates (a) systemic and peri-articular inflammation, (b) bone and cartilage degradation, and (c) arthritis-related body weight loss. Treatment with folate-hapten conjugates is comparable to methotrexate, etanercept, anakinra, and celecoxib at alleviating the symptoms of arthritis. We conclude that reduction of activated macrophages by folate-targeted immunotherapy can ameliorate the symptoms of arthritis in two rodent models of the disease.
Paulos
Chrystal M
CM
Department of Chemistry, 560 Oval Drive, 1393 Brown Bldg, Purdue University, West Lafayette, IN 47907-1175, USA. paulosc@mail.nih.gov
Varghese
Bindu
B
Widmer
William R
WR
Breur
Gert J
GJ
Vlashi
Erina
E
Low
Philip S
PS
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D005492:Folic Acid / Q000276:immunology*; D005494:Folic Acid Deficiency; D007167:Immunotherapy; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D011917:Rats, Inbred Lew; D016474:Weight-Bearing
D005492:Folic Acid