Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration.
Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the efficacy of UC-II (10 mg/day) in five female subjects (58-78 years) suffering from significant joint pain. Significant pain reduction including morning stiffness, stiffness following periods of rest, pain that worsens with use of the affected joint and loss of joint range of motion and function was observed. Thus, UC-II may serve as a novel therapeutic tool in joint inflammatory conditions and symptoms of OA and RA.
Bagchi
D
D
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, Nebraska 68178, USA.
Misner
B
B
Bagchi
M
M
Kothari
S C
SC
Downs
B W
BW
Fafard
R D
RD
Preuss
H G
HG
D000284:Administration, Oral; D000368:Aged; D001168:Arthritis / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D024043:Collagen Type II / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy; D010147:Pain Measurement; D010865:Pilot Projects; D016896:Treatment Outcome
D024043:Collagen Type II