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University of Tennessee, Memphis, USA.
OBJECTIVE: |
Joint inflammation in juvenile rheumatoid arthritis (JRA) is sometimes associated with an autoimmune response to type II collagen (CII), a cartilage-specific protein. To test the hypothesis that down-regulation of autoimmunity to CII can be accomplished in JRA by oral administration of CII, an open-label study of CII was performed in 9 patients with JRA....
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RESULTS: |
Eight patient trials met the criteria for clinical improvement outlined by Giannini and coworkers in 1997. None of the patients had any side effects from the treatment. In 6 of the 8 patients who improved, interferon-gamma production decreased after oral CII therapy, correlating with clinical improvement, while 6 patients had increases in levels of transforming growth factor beta3.
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CONCLUSION: |
These results are encouraging.
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Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
OBJECTIVE: |
Oral administration of cartilage-derived type II collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patients with RA....No treatment-related adverse events were detected. The efficacy seen with the lowest dosage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administered autoantigens preferentially induce disease-suppressing regulatory cells.
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CONCLUSION: |
Positive effects were observed with CII at the lowest dosage tested, and the presence of serum antibodies to CII at baseline may predict response to therapy. No side effects were associated with this novel therapeutic agent.
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Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea.
Induction of oral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA). Oral administration of type II collagen (CII) has been proven to improve signs and symptoms in RA patients without troublesome toxicity. To investigate the mechanism of immune suppression mediated by orally administered antigen, we examined changes in serum IgG subtypes and T-cell proliferative responses to CII, and generation of IL-10-producing CD4+CD25+ T-cell subsets in an animal model of collagen-induced arthritis (CIA).....
These data suggest that when these IL-10-producing CD4+CD25+ T cells encounter CII (Collagen type II) antigen in affected joints they become activated to exert an anti-inflammatory effect.
Department of Rheumatology, University Hospital Jean Minjoz, Bd A. Fleming, F-25030 Besancon Cedex, France.
Oral tolerance (OT) consists of the oral administration of antigens (Ag) that could alter the response of the immune system...In Rheumatoid Arthritis, 4 trials of oral type II collagen (CII) in RA have been published. Taken together, these studies suggested that oral CII in RA gave a trend toward clinical improvement...
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
OBJECTIVE: |
The objective of this study was to investigate the effect of the oral administration of type II collagen (CII) on pro-inflammatory mediator production by synoviocytes in rats with adjuvant arthritis (AA). Sprague-Dawley rats were fed with bovine CII either before immunization with Complete Freund's adjuvant (CFA) or after initiation of arthritis....
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CONCLUSION: |
We conclude that oral administration of CII (type II collagen) had prophylactic and therapeutic effects on AA and over-production of IL-1, TNF, NO and MDA by synoviocytes was suppressed. Bystander active suppression may be the main mechanism of oral CII in the suppression of synoviocyte function.
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Guy's Kings, Hospital School of Medicine, King's College, London, UK.
OBJECTIVE: |
Previous randomized controlled trials for treatment of rheumatoid arthritis (RA) with acid-soluble chicken and bovine type II collagen (CII) have produced conflicting results. This randomized, double-blind, controlled trial examined the therapeutic effect of bovine CII tablets in RA....
There were no side effects associated with CII treatment.
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CONCLUSION: |
Treatment with 0.5 mg/day of bovine CII is well tolerated and produces small, but significant, disease improvement in Rheumatoid Arthritis....The difference between our results and those of other trials may relate to the dose, species, and formulation of the CII.
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CEPROCOR (Centro de Excelencia en Productos y Procesos de Cordoba), Argentina.
We evaluated the efficacy and safety of orally administered bovine tracheal type II collagen (CGII) in the treatment of rheumatoid arthritis (RA). Twenty RA patients received 0.5 mg/day of CGII for 12 weeks. Eighteen of them had improvements in the clinical parameters studied (swollen and tender joint counts, 15-m walking time, duration of morning stiffness, and physician's global assessment of disease activity)....
Although a placebo effect cannot be discounted, the oral administration of bovine tracheal CGII induced clinical benefits in 90% of the patients, without the side effects usually associated with treatment. This is the first study showing that feeding CGII can induce reductions in RF and TNF-alpha.
Department of Microbiology, Saga Medical School, Japan.
Oral administration of type II collagen (CII) has been shown to suppress collagen-induced arthritis (CIA) in experimental animals...
Thus, the neutralization of IL-4 by an anti-IL-4 Ab appears to be effective in blocking suppression of CIA by oral administration of CII, suggesting that IL-4 may be critically involved in its suppression.
Department of Orthopedic Surgery, Kansai Medical University.
The correlation between the efficacy of type II collagen (C II) treatment of the rheumatoid arthritis (RA) and the existence of HLA-DRB 1 * 0405 allele was investigated in two groups of patients....
We concluded that oral C II could have a therapeutic efficacy in RA patients with HLA-DRB 1 * 0405 allele.
Department of Microbiology, Saga Medical School, Japan.
The present study was designed to investigate the efficacy of oral administration of type II collagen (CII) on non-specifically induced chronic arthritis in rats, induced by intra-articular injection of a mineral oil, squalene. When CII was fed before injection of squalene, no chronic arthritis developed.
Feeding CII after the induction of arthritis was also effective in suppressing the progression of chronic joint inflammation. In rats fed and primed with CII, there was a decrease in proliferative responses to CII. Arthritis induced by the mineral oil was markedly suppressed by the spleen cells from animals fed CII. These results indicate that non-specifically induced arthritis may be downregulated by the oral administration of CII
Brigham and Women's Hospital, Boston, MA 02115, USA.
OBJECTIVE: |
To assess the effect of orally administered type II collagen (CII) in antigen-induced arthritis (AIA)...
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RESULTS: |
Joint swelling was significantly reduced at a dose of 3 micrograms and 30 micrograms of CII...
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CONCLUSION: |
Oral CII can suppress arthritis in an animal model in which immunity to collagen does not play a role. The effect is dose dependent and occurs at lower doses of CII. These results demonstrate the biologic relevance of bystander suppression associated with oral tolerance, and the potential use of this approach to treat human inflammatory joint disease.
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Department of Medicine, Beth Israel Hospital, Boston, MA.
Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease....
Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.
Infection & Immunity Group, King's College London, U.K.
The oral administration of CII by gavage to WA/KIR rats before a conventional arthritogenic challenge with bovine CII in FIA reduced the incidence (by 23%) and delayed the onset of collagen-induced arthritis in about 50% of the animals...
These studies show that the oral administration of CII alters the subsequent immune response to the arthritogenic challenge and indicate that this oral tolerance of CII is due, not to clonal deletion or anergy, but rather to an antigen-driven active suppression mechanism...
Results of a Study Evaluating the Use of a Dietary Supplement Formula in the Management of Age-Related Skin Changes in Women with Moderate to Severe Wrinkling of the Periorbital Area
Irwin Kantor, MD, FAAD, Louise A. Donikyan, DO, Randi Simon, BS
RTL, Inc., Hackensack, New Jersey
Bernd Wollschlaeger, MD
Clinical Assistant Professor of Medicine and Family Medicine,
University of Miami School of Medicine, Miami, Florida
CONTEXT: |
The relationship between dietary supplementation and the repair of aging skin is unclear.
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OBJECTIVE: |
To assess the safety and efficacy of a dietary formulation for the improvement of age-related degenerative skin changes in women.
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METHODS: |
Using a blinded, randomized, parallel design, a total of 40 women, ages 35-65 years were enrolled and divided into approximately balanced groups with 38 women completing this eight-week, four-visit study. Recommended daily doses of the study product, a dietary collagen formulation (Toki), were 7.5 g (given to Group A), and 8.5 g (given to Group B). Both investigator and subjects assessed skin wrinkling and other skin characteristics in the periorbital area as well as overall facial aging.
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MAIN OUTCOME MEASURES: |
Safety and efficacy of a dietary collagen formulation when used to improve periorbital wrinkling, aging, sagging and puffiness and periorbital overall facial aging.
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RESULTS: |
The consumption of the dietary collagen formulation resulted in a highly statistically significant improvement in periorbital wrinkling, in periorbital aging and in periorbital overall facial aging. The investigator's mean global improvement scores of overall facial aging as compared to baseline photographs were highly significant.
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CONCLUSION: |
In women with age-related skin changes, a dietary collagen formulation (Toki) significantly improved periorbital wrinkling, periorbital aging, and periorbital overall facial aging with minimal adverse effects.
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