Treatment of Th1Mediated Autoimmune Diseases

We conducted the first anti-IFN-y therapy in Th-1-mediated diseases together with several clinics using a polyclonal anti-IFN-y antibody (both IgG and F(ab')2 antibody fragments) and in some cases, for comparison, a polyclonal anti-TNF-a. The antibodies were given intramuscularly once or twice daily for 5-6 days. Our studies include placebo-controlled, double-blind studies in patients with rheumatoid arthritis unresponsive to standard treatments (Sigidin et al. 2001) and in patients with...

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Isomallotochromanol and isomallotochromene Luteolin Rocaglamides Sanggenon C Sphondin Silymarin Saucerneols Sauchinone and Manassantins Wedelolactone Yakuchinones A and B Benzopyrene Rotenone Chlorophyll catabolite Pheophorbide A Iridoid glycoside Aucubin Others a-Lipoic acid Astaxanthin Germinated barley S-allylcysteine Vitamin C Vitamin E Oxoacanthospermoldes Parthenolide Pristimerin Triptolide (PG 490) Ursolic acid Alkaloids Cepharanthine Conophylline Morphine and its analogs Tetrandine...

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Histological examination of the skin in IL-1Ra- - mice. A Hematoxylin and eosin staining of the ear pinna of a normal 20-week-old WT mouse. B An affected IL-1Ra- - mouse at 20 weeks of age. The epidermis becomes thickened and hypertrophic associated with hyperkeratosis of the skin. Massive infiltration of neutrophils into the epidermis and dermis are observed in IL-1Ra- - mouse Fig. 6. Histological examination of the skin in IL-1Ra- - mice. A Hematoxylin and eosin staining of the ear...

IL15 in Psoriasis and Psoriatic Arthritis

IL-15 exhibits a plausible bioactivity profile in skin inflammation and has been detected in high levels in a range of inflammatory dermatoses. Thus, keratinocytes express both IL-15 and IL-15Ra, suggesting a role in autocrine regulation of keratinocytes in dermal inflammatory responses (Ruckert et al. 2000). Dermal IL-15 is upregulated by UVB irradiation and overexpression is associated with cutaneous malignancy (Mohamadzadeh et al. 1995). IL-15 has also been reported in bullous lesions,...

Other Th1Mediated Skin Diseases in Which Testing of Anticytokine Therapy Is Warranted

Other skin diseases that appear to involve a Th-1-mediated immune response include seborrheic dermatitis (SD), rosacea, oral lichen planus, and dermatophytosis. SD has upregulated expression of proinflamma-tory cytokines in skin biopsies of SD lesions (Molinero et al. 2003). T-cell subsets are also found in the dermal infiltrates of rosacea lesions (Rufli and Buchner 1984), and IFN-y-producing cells are found in dermatophytosis (Koga et al. 2001). In oral lichen planus, mononuclear cells...

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Splenic CD4+T cells (5 x 107) were transferred into BALB.B-scid scid mice, and the development of arthritis was inspected after 12 weeks * p < 0.05 vs TNFa+ +-IL-1Ra- - mice by x2 test ** p < 0.01 vs TNFa+ +-IL-1Ra- - mice by x2 test Splenic CD4+T cells (5 x 107) were transferred into BALB.B-scid scid mice, and the development of arthritis was inspected after 12 weeks * p < 0.05 vs TNFa+ +-IL-1Ra- - mice by x2 test ** p < 0.01 vs TNFa+ +-IL-1Ra- - mice by x2 test suggest that TNFa...

References

Albers R, Bol M, Bleumink R, Willems AA, Pieters RH (2003) Effects of supplementation with vitamins A, C, and E, selenium, and zinc on immune function in a murine sensitization model. Nutrition 19 940-946 Arca E, Musabak U, Akar A, Erbil AH, Tastan HB (2004) Interferon-gamma in alopecia areata. Eur J Dermatol 14 33-36 Aurelian L, Ono F, Burnett J (2003) Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) a viral disease with an autoimmune component. Dermatol Online J 9 1 Barker JN,...

Treatment of Th1Mediated Autoimmune Skin Diseases Using AntiIFNy

We used anti-IFN-y in patients with psoriasis vulgaris, alopecia areata, vitiligo, acne vulgaris, and herpes simplex type 1, and plan to expand the trials using a humanized monoclonal antibody. Trials are also planned for testing the treatment in other Th-1-mediated skin diseases, including seborrheic dermatitis, rosacea, oral lichen planus, and dermatophyto-sis, which are discussed in the following sections. In most cases, we used two methods of delivery of the antibody intradermal injection...

HDAC Inhibitors in Models of Inflammatory Diseases 321 Models of Lupus Erythematosus

An unexpected finding of HDAC inhibitors was the reduction in disease severity of models of murine autoimmune disease. The mouse model for systemic lupus erythematosus is the lpr lpr mouse that develops a spontaneous disease characterized by nephritis, proteinuria and early death. Trichostatin A was injected into these mice before the onset of significant disease for 5 weeks. Because trichostatin A in water is insoluble, the vehicle was also used for 5 weeks of treatment. Trichostatin A...

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Although TNF is a potent activator of AP-1, no specific blocker of AP-1 activation has yet been described. However, most phytochemicals that suppress NF-kB activation also suppress AP-1 activation (Manna and Aggarwal 2000 Manna et al. 2000 Torii et al. 2004). 10.3.3 Suppression of TNF-Induced P38 MAPK Activation TNF is one of the most potent activators of p38 MAPK (Lee et al. 1994). This activation is specifically inhibited by SB203580 (Henry et al. 1998 Kumar et al. 1997). Campbell et al....