minocycline and Uveitis

Autoimmune uveitis induces a serious pathological and inflammatory response in the retina/choroid and results in vision impairment and blindness. Here, we report a minocycline (Mino) nanocomposite-loaded hydrogel offering a high drug payload and sustained drug release for the effective control of ocular inflammation via a single subcutaneous injection. In the presence of divalent cations (i.e., Ca

Topics: Animals; Hydrogels; Inflammation; Injections, Subcutaneous; Minocycline; Nanogels; Polyethylene Glycols; Rats; Uveitis

Noninfectious (autoimmune and immune-mediated) uveitis is an ocular inflammatory disease which can lead to blindness in severe cases. Due to the potential side effects of first-line drugs for clinical uveitis, novel drugs and targets against uveitis are still urgently needed. In the present study, using rat experimental autoimmune uveitis (EAU) model, we first found that minocycline treatment can substantially inhibit the development of EAU and improve the retinal function by suppressing the retinal microglial activation, and block the infiltration of inflammatory cells, including Th17, into the retina by decreasing the major histocompatibility complex class II (MHC II) expression in resident and infiltrating cells. Moreover, we demonstrated that minocycline treatment can remodel the gut microenvironment of EAU rats by restoring the relative abundance of Ruminococcus bromii, Streptococcus hyointestinalis, and Desulfovibrio sp. ABHU2SB and promoting a functional shift in the gut via reversing the levels of L-proline, allicin, aceturic acid, xanthine, and leukotriene B4, and especially increasing the production of propionic acid, histamine, and pantothenic acid. At last, we revealed that minocycline treatment can significantly attenuate the progression of EAU after inflammation onset, which may be explained by the role of minocycline in the remodeling of the gut microenvironment since selective elimination of retinal microglia on the later stages of EAU was shown to have little effect. These data clearly demonstrated that inhibition of microglial activation and remodeling of the gut microenvironment can suppress the development and progression of experimental autoimmune uveitis. Considering the excellent safety profile of minocycline in multiple clinical experiments, we suggest that minocycline may have therapeutic implications for clinical uveitis.

Topics: Animals; Autoimmune Diseases; Cellular Microenvironment; Disease Models, Animal; Gastrointestinal Microbiome; Histocompatibility Antigens Class II; Male; Microglia; Minocycline; Rats; Rats, Inbred Lew; Retina; Th17 Cells; Uveitis

Uveitis is a serious inflammatory disease of the uvea, frequently leading to visual impairment and irreversible blindness. Here, we investigated the anti-inflammatory effect of minocycline on rat endotoxin-induced uveitis (EIU) and retinal inflammation.. For in vivo studies, the rat EIU model was induced with intravitreal injection of lipopolysaccharide (LPS). Minocycline was administered intraperitoneally 2 h before and after the LPS injection. The severity of the ocular inflammation was evaluated with slit-lamp photography, aqueous humor cell counting, protein quantitative determination, and histological analysis. Retinal microglia were labeled with a fluorescent dye 4Di-10ASP. Microglial activity and inflammatory cytokine production were analyzed with immunofluorescence and real-time PCR. For the in vitro studies, BV-2 microglia cells were stimulated with LPS or cotreated with minocycline for 6 h. Toll-like receptor (TLR) 2/4 levels were determined with real-time PCR and western blotting.. The LPS-challenged eyes displayed severe inflammation in all ocular structures, including a large number of anterior chamber cells, fibrin exudation, hypopyon, and infiltrated inflammatory cells in the vitreous and retina. Immunostaining of the retinal whole-mounts also revealed numerous retinal microglia were activated promptly, and then more and more peripheral leukocytes were recruited and infiltrated in the LPS-injected retinas. Additionally, the production of tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL-2), interleukin-1 beta (IL-1β), and IL-6 was dramatically increased. However, minocycline treatment strongly inhibited microglia activation, decreased inflammatory cytokine production, prevented peripheral inflammatory cell recruitment, and significantly attenuated ocular inflammation. Finally, we demonstrated the mechanism of the microglia inactivation effect of minocycline is via suppression of TLR4 signaling.. This study indicates minocycline is far beyond an antibiotic. It not only attenuates rat EIU but also inhibits retinal inflammation through inactivating microglia, inhibiting inflammatory cell recruitment and inflammatory cytokine production.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Down-Regulation; Endotoxins; Inflammation; Leukocytes; Mice; Microglia; Minocycline; Rats; Retina; Signal Transduction; Toll-Like Receptor 4; Uveitis

The purpose of this study was to evaluate the ocular distribution of intravenously administered tigecycline in a rabbit uveitis model.. Tigecycline, which has a broad spectrum of activity against many gram-positive, gram-negative, and anaerobic organisms, was given intravenously to rabbits at 7 mg/kg of body weight starting 24 h after induction of uveitis by intravitreal endotoxin injection. Tigecycline concentrations were determined by high performance liquid chromatography-mass spectrometry (LC-MS/MS) assay in the aqueous humor, vitreous humor, and plasma 1, 3, 6, and 24 h after administration of a single dose.. The maximum concentrations were found within 1 h after the end of the intravenously given tigecycline, and were 1,308.60 ± 301.76 ng/mL in plasma, 181.40 ± 51.32 ng/mL in vitreous humor and 145.00 ± 55.29 ng/mL in aqueous humor of the inflamed eye. After 24 h, no drug was detectable in the aqueous and vitreous of the normal eyes, whereas small amounts of drug were detectable in inflamed eyes and in plasma.. Tigecycline did not reach therapeutically significant levels in the aqueous and the vitreous humor of rabbit eyes. The findings suggest a limited role for intravenously administered tigecycline in the treatment of bacterial endophthalmitis.

Topics: Animals; Anti-Bacterial Agents; Aqueous Humor; Biological Availability; Chromatography, High Pressure Liquid; Disease Models, Animal; Escherichia coli; Injections, Intravenous; Lipopolysaccharides; Minocycline; Rabbits; Tandem Mass Spectrometry; Tigecycline; Uveitis; Vitreous Body

Vitamin D research is discussed in light of the hypothesis that the lower average levels of vitamin D frequently observed in autoimmune disease are not a sign of deficiency. Instead, it is proposed that the lower levels result from chronic infection with intracellular bacteria that dysregulate vitamin D metabolism by causing vitamin D receptor (VDR) dysfunction within phagocytes. The VDR dysfunction causes a decline in innate immune function that causes susceptibility to additional infections that contribute to disease progression. Evidence has been accumulating that indicates that a number of autoimmune diseases can be reversed by gradually restoring VDR function with the VDR agonist olmesartan and subinhibitory dosages of certain bacteriostatic antibiotics. Diseases showing favorable responses to treatment so far include systemic lupus erythematosis, rheumatoid arthritis, scleroderma, sarcoidosis, Sjogren's syndrome, autoimmune thyroid disease, psoriasis, ankylosing spondylitis, Reiter's syndrome, type I and II diabetes mellitus, and uveitis. Disease reversal using this approach requires limitation of vitamin D in order to avoid contributing to dysfunction of nuclear receptors and subsequent negative consequences for immune and endocrine function. Immunopathological reactions accompanying bacterial cell death require a gradual elimination of pathogens over several years. Practical and theoretical implications are discussed, along with the compatibility of this model with current research.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Reactive; Arthritis, Rheumatoid; Autoimmune Diseases; Bacterial Infections; Calcifediol; Calcitriol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Imidazoles; Minocycline; Psoriasis; Receptors, Calcitriol; Sarcoidosis; Scleroderma, Systemic; Sjogren's Syndrome; Spondylitis, Ankylosing; Tetrazoles; Thyroid Diseases; Uveitis

Cogan's syndrome is a rare clinical entity defined by the association of a nonsyphilitic interstitial keratitis and vestibuloauditory dysfunction, typically Menière's disease-like; the condition has been reported in association with a variety of cutaneous diseases. We now report a case of pyoderma gangrenosum complicating Cogan's syndrome in a 57-year-old woman, which then healed dramatically, as more interestingly did the associated uveitis with minocycline therapy.

Topics: Ataxia; Deafness; Female; Humans; Keratitis; Meniere Disease; Middle Aged; Minocycline; Nausea; Pyoderma Gangrenosum; Syndrome; Uveitis; Vertigo; Vomiting

Topics: Anti-Bacterial Agents; Arthritis, Rheumatoid; Humans; Minocycline; Randomized Controlled Trials as Topic; Scleritis; Uveitis

A 14-year-old boy was admitted to our hospital complaining of dull headache, high fever and decreased visual acuity of his left eye. Physical examination on admission revealed nuchal rigidity, positive Kernig's sign, slight hyperreflexia of deep tendon reflex, and decreased visual acuity of his left eye to 0.1. The chest was clear to percussion and auscultation, and no abnormal findings was observed on chest x-ray examination. On laboratory examination, leukocytosis (12,800/mm3) and increased erythrocyte sedimentation rate (83mm/hr) was observed. Cerebrospinal fluid (CSF) examination showed pleocytosis (308/3, mono 286, poly 22) and slight elevation of protein without decrease of glucose content (52mg/dl). On ophthalmologic examination, characteristic anterior and posterior uveitis was found in both eyes, more on the left. Antibody titer to psittaci was significantly elevated in both serum and CSF in his clinical course, therefore, this case was diagnosed as psittacosis meningitis complicated with uveitis. Minocycline (200mg/day) was administered from the 30th hospital day. The effect of this drug was dramatic, and fever and dull headache rapidly disappeared. In addition, fundus oculi examination on the 85th hospital day, revealed no abnormality in his eyes, and his visual acuity returned to normal level (1.0). This case was considered to be extremely rare case of psittacosis, because in addition to meningitis, the patient complicated with uveitis without any respiratory signs and symptoms.

Topics: Adolescent; Humans; Male; Meningitis; Meningitis, Aseptic; Minocycline; Psittacosis; Uveitis