tetracycline and Autoimmune-Diseases

While the biology of the pathogenesis of scleroderma is continually being better understood, there still is no single agent or therapeutic combination that has a clear impact on the disease process. Traditional medications (colchicine, potassium aminobenzoate (potaba), D-penicillamine) are disappointing in clinical practice despite anecdotal evidence of benefit. Furthermore, the most popular traditional drug, D-penicillamine, failed to clearly show benefit when tested in a well-designed clinical trial comparing conventional high dose with a very low dose (125 mg po. every other day [corrected]) [1]. Currently, most success in managing scleroderma and improving quality of life is secondary to organ-specific therapy, such as management of a renal crisis with an ACE inhibitor, treatment of Raynaud's phenomenon with calcium channel blockers, or control of serious gastrointestinal reflux disease with a proton pump inhibitor. In this review we will focus on novel therapies that are currently being tested in the treatment of scleroderma and have the potential of modifying the disease process and overall clinical outcome. We have attempted to review the rationale for each agent, recognising that its true biological effect will only be determined in clinical trials.

Topics: Autoimmune Diseases; Bone Marrow Transplantation; Cysteine; Humans; Interferon-gamma; Nitric Oxide; Piperidines; Prostaglandins; Quinazolines; Quinazolinones; Relaxin; Scleroderma, Systemic; Tetracycline; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

After some initial disappointments, the field of gene therapy is now gaining confidence and momentum. Recent improvements in gene transfer techniques promise targeted and supra-threshold levels of transgene expression leading to the desired therapeutic effects. This increase in optimism has spread to thefield of diabetes research. Firstly, the recent developments in gene transfer techniques are now being tested on the pancreatic insulin producing beta-cell. For many gene therapy strategies in the treatment of diabetes, transfection of insulin producing cells is a prerequisite. Secondly, if efficient and safe vectors that transduce beta-cells in vivo or ex vivo are made available, autoimmune beta-cell destruction in type 1 diabetes could be prevented. In this strategy, it is envisaged that gene therapy will protect the remaining beta-cell mass in newly diagnosed diabetics or pre-diabetic individuals at a high risk of becoming diabetic from autoimmune destruction. Thirdly, attempts are being made to genetically engineer cells to become artificial beta-cells. Such cells could conceivably compensate for the lost endogeneous alpha-cell mass and restore a regulated insulin secretion. This review will attempt to predict the future of gene therapy in the treatment of diabetes.

Topics: Adjuvants, Immunologic; Animals; Apoptosis; Autoantigens; Autoimmune Diseases; Cell Division; Cell Line, Transformed; Cell Survival; Cytokines; Diabetes Mellitus, Type 1; DNA, Recombinant; Fas Ligand Protein; Fibroblasts; Genetic Therapy; Genetic Vectors; Graft Rejection; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Islets of Langerhans Transplantation; Membrane Glycoproteins; Mice; Mice, Transgenic; Pancreatic Ducts; Perforin; Pituitary Neoplasms; Pore Forming Cytotoxic Proteins; Proinsulin; Protein Processing, Post-Translational; Tetracycline; Transfection; Transplantation, Heterologous; Transplantation, Homologous; Tumor Cells, Cultured

Members of the adeno-associated virus (AAV) family are good candidates for the treatment of ocular diseases because of their relative lack of pathogenicity. We studied the effect of intraocular injection of AAV2-viral IL-10 (vIL-10) on retinal S-antigen-induced experimental autoimmune uveoretinitis (EAU) in Lewis rats. We demonstrated that AAV2/2-GFP injected into the vitreous body transduced the iris and ciliary body, or anterior uvea, and the retina. We showed that intravitreal injection of the AAV2/2-tetON-vIL-10 construct achieved detectable levels of vIL-10 mRNA and protein within the eye and was effective in protecting the rat retina against destruction. This protection was dependent on the level of vIL-10 present in the aqueous humor/ vitreous body. Intravitreal injection of the same construct encased within an AAV5 shell, AAV2/5-tetONvIL- 10, did not confer any degree of protection. It appeared that the AAV2/5 vectors did not transduce the anterior uvea, the site at which inflammatory cells first localize in EAU, nor the ganglion cell layer; induced low expression of vIL-10 mRNA; and did not achieve detectable levels of transgene expression in the aqueous humor/vitreous body. Local treatment with AAV2/2-tetON-vIL-10 did not dampen the systemic immune response, as determined by S-antigen-specific lymphocyte proliferation. Our results show that local intravitreal injection of AAV2/2 is an effective means by which to deliver immunoregulatory molecules into the eye during uveitis, a chronic human ocular disease.

Topics: Animals; Aqueous Humor; Arrestin; Autoimmune Diseases; Cell Proliferation; Dependovirus; Disease Models, Animal; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Green Fluorescent Proteins; Humans; Interleukin-10; Lymphocytes; Male; Rats; Rats, Inbred Lew; Retina; Retinitis; Tetracycline; Uveitis

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Autoimmune Diseases; Bismuth; Drug Therapy, Combination; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; L-Lactate Dehydrogenase; Metronidazole; Omeprazole; Organometallic Compounds; Purpura, Thrombocytopenic, Idiopathic; Salicylates; Tetracycline

A combination of niacinamide and tetracycline was used to treat 31 dogs with various autoimmune skin diseases (discoid lupus erythematosus, pemphigus foliaceus, pemphigus erythematosus, and bullous pemphigoid). Of the 20 dogs with discoid lupus erythematosus, 70% had excellent or good response to treatment. Serious side effects were not noticed in any dog.

Topics: Animals; Autoimmune Diseases; Dog Diseases; Dogs; Drug Combinations; Female; Lupus Erythematosus, Discoid; Niacinamide; Pemphigoid, Bullous; Pemphigus; Skin Diseases; Tetracycline

Lyme spirochaetal disease (LSD) is a complex multisystem disorder which has been recognized as a separate entity due to its close geographic clustering of affected patients. The study aimed at evaluating the clinical and immunological features of LSD with chronic symptoms of meningoradiculitis, carditis and pauciarticular arthritis. Six patients with LSD and erosive arthritis who developed an increase of serum IgM rheumatoid factor (RF) which correlated with the inflammatory activity of the disease are described in detail. Besides raised IgG antibody titers to Borrelia burgdorferi (B. burgd.) antigen measured by ELISA technique, circulating immune complexes, antinuclear antibodies (ANA) and RF measured by laser nephelometric immunoassay were detected. Increased ANA and RF antibody rates suggest that LSD may closely be linked with transient autoimmune phenomena. Thus, in some cases, B. burgd. antigens might be able to produce a strong polyclonal B-cell stimulation, hence leading to an unspecific autoimmune reaction. But the question remains if transient unspecific autoimmune reactions actually take part in the pathogenesis of LSD.

Topics: Adult; Arthrography; Autoimmune Diseases; Drug Therapy, Combination; Female; Humans; Lyme Disease; Male; Middle Aged; Penicillins; Rheumatoid Factor; Tetracycline; Time Factors

The various forms of aphthous stomatitis and Behcet syndrome share common signs that were discussed during a conference workshop. Four markers should be considered in determining the presence of these diseases: hematologic abnormalities, HLA, antibody responses, and immune complexes.

Topics: Animals; Autoimmune Diseases; Behcet Syndrome; Folic Acid Deficiency; Humans; Immunity, Cellular; Iron Deficiencies; Levamisole; Recurrence; Stomatitis, Aphthous; Tetracycline; Vitamin B 12 Deficiency

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Humans; Stomatitis, Aphthous; Tetracycline