minocycline and Arthritis

Irreversible degradation of articular cartilage is a major feature of the arthritides, and its prevention is a therapeutic goal which has been difficult to achieve. Enzymes from the matrix metalloproteinase and ADAMTS (a disintegrin, a metalloproteinase, and thrombospondin motif) families are key mediators of cartilage extracellular matrix destruction. Inhibition of metalloproteinase activity is therefore a conceptually attractive therapeutic strategy, although clinical efficacy has not yet been demonstrated. This review outlines the biology behind metalloproteinases as drug targets in the arthritides, and poses important questions for the future design of such therapies.

Topics: ADAM Proteins; ADAM17 Protein; Animals; Arthritis; Arthritis, Experimental; Cartilage, Articular; Drug Design; Drug Evaluation, Preclinical; Extracellular Matrix Proteins; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Mice; Minocycline; Protease Inhibitors

Minocycline is the most widely prescribed systemic antibiotic for the management of acne. In the past several years, increasing attention has been paid to the drug, both for its potential use as a disease-modifying antirheumatic agent and for its propensity to engender untoward autoimmune reactions, including serum sickness-like disease, drug-induced lupus, and autoimmune hepatitis. This paper reviews the evidence for minocycline as an anti-inflammatory and immunomodulatory agent, its utility in the treatment of rheumatoid arthritis, and the spectrum of adverse reactions that have been ascribed to the drug in the past 5 years.

Topics: Acne Vulgaris; Animals; Anti-Bacterial Agents; Arthritis; Arthritis, Rheumatoid; Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Female; Humans; Lupus Erythematosus, Systemic; Male; Minocycline; Vasculitis

Pain is a sensory experience of a complex physiological nature in which is not only involved the nervous system. Among its many features is the development of chronic pain that is more complicated to treat because of the central somatization processes involved, becoming inefficient treatments used in other forms of pain. Among them is the role of glial cells, whose participation is such that some authors have proposed to chronic pain as a gliopathy. Because of this, the drug target of possible treatments focuses on modulating nociceptive response affecting transduction into the central nervous system through affecting synapses in the dorsal horn of the spinal cord. Solid lipid nanoparticles enter the central nervous system, protecting the drug, and in addition to the advantage of having greater absorption surface, all factors that improve drug activity. This work is based on the development and characterization of lipid nanoparticles of solid phase incorporating two antibiotics, minocycline, and ciprofloxacin with antinociceptive properties and challenged them with a rat monoarthritis model using Sprague-Dawley adult male rats. The solid lipid nanoparticles were prepared to modify the lipid, and surfactant amounts to obtain the best encapsulation capacity of the antibiotics, size and z potential. By using the Randall-Selitto test, we measured its pharmacological efficiency as an anti-inflammatory and measuring the time span the antibiotics are active. The encapsulated antibiotics were at least 50% more efficient than the antibiotic alone, and that is possible to measure anti-inflammatory activity up to seven days after the antibiotic application. The former is important for example, in the veterinary field, since a single application of the antibiotic will be necessary for the complete treatment, avoiding excessive stress for the animals. We can conclude that antinociceptive antibiotics encapsulation is a very effective, environmentally safe and inexpensive method for improving the pharmacological efficiency and time span the antibiotics are acting. Since these antibiotics are both anti-microbial and antinociceptive, his use in the field of veterinary presents the advantage of being adequate in single doses, with the saving of time and stress to the animals under treatment.

Topics: Analgesics; Animals; Anti-Bacterial Agents; Arthritis; Chronic Disease; Ciprofloxacin; Delayed-Action Preparations; Drug Carriers; Drug Liberation; Lipids; Male; Minocycline; Nanoparticles; Rats; Rats, Sprague-Dawley

Chronic systemic inflammation induces age-dependent differential phenotypic changes in microglia and astrocytes, yielding an anti-inflammatory cell phenotype in young rats and a proinflammatory cell phenotype in middle-aged rats. These observations prompted further investigation of the functional outcomes of the resultant differential microglial phenotypic changes. The present study examined the effects of age-dependent differential microglial phenotypic changes following chronic systemic inflammation on the formation of the post-tetanic potentiation (PTP) and long-term potentiation (LTP) in the hippocampus. Microglia formed a proinflammatory cell phenotype to express ED1 and interleukin-1β (IL-1β) in the hippocampal CA1 region of middle-aged rats, but not in young rats following the establishment of adjuvant arthritis (AA). Furthermore, AA induced deficits in the formation of LTP in the Schaffer collateral-CA1 synapses of middle-aged rats, but not in young rats. On the other hand, the formation of PTP was impaired in both young and middle-aged AA rats. Minocycline, a known inhibitor of microglial activation, was systemically administered to middle-aged AA rats significantly restoring the mean magnitudes of both PTP and LTP. The mean expression levels of ED1 and IL-1β were significantly suppressed. These observations strongly suggest that chronic systemic inflammation induces deficits in the hippocampal LTP in middle-aged rats through neuroinflammation mainly induced by microglia.

Topics: Aging; Animals; Anti-Bacterial Agents; Arthritis; Astrocytes; Disease Models, Animal; Female; Hippocampus; Inflammation; Interleukin-1beta; Long-Term Potentiation; Microglia; Minocycline; Rats; Rats, Inbred Lew; Synapses

Minocycline-induced pigmentation of bone (black bone) is well described in tooth-bearing intra-oral bone, but is less known in periarticular bone in patients who have undergone total joint arthroplasty. On a retrospective basis, we investigated the short-term clinico-radiological results of total joint arthroplasties in which the patient developed minocycline-induced periarticular black bone.. We found 5 cases (0.08%), in 4 patients, of periarticular bone pigmentation revealed during total joint arthroplasties (2 hips, 2 knees, and 1 ankle) in our series of total joint surgeries (6,548 cases) over a 10-year time period in our 3 institutes. Their mean age was 56 years at surgery. All patients had received long-term minocycline treatment. Mean dosage and duration of minocycline was 160 mg/day and 2.2 years, respectively. Minocycline had been prescribed for reactive arthritis (one), rheumatoid arthritis (two) and late infection after total joint arthroplasty (two patients). Mean follow-up period was 3.4 years after the surgeries.. All cases had black or brown pigmentation in the periarticular bones during the surgery. There was no pigmentation in the cartilage or soft tissues of the joints. The mean Japanese Orthopaedic Association (JOA) score or Japanese Society for Surgery of the Foot (JSSF) scale for rheumatoid arthritis foot and ankle joints at latest follow-up (case 1, 66; case 2, 87; case 3, 77; case 4, 77; case 5, 80) improved compared to those of pre-surgery (case 1, 47; case 2, 45; case 3, 55; case 4, 34; case 5, 55). No implant loosening was noted on radiographic examination during the follow-up period. No abnormal bone formation, bone necrosis, hemosiderin deposition, malignancy or metallic debris was found on histological examination.. No clinico-radiological symptoms of total joint arthroplasties showed in the patients with minocycline-induced periarticular black bone in the short-term. Systemic minocycline treatment has the potential to induce significant black pigmentation of many tissues. In particular, minocycline-induced pigmentation of periarticular bone may be accelerated by inflammation due to rheumatic or pyogenic arthritis. Surgeons should recognize the risk of bone pigmentation in inflamed joints due to the systemic treatment of minocycline and explore its influence on periarticular bone and total joint arthroplasty in the long-term.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Arthritis; Arthroplasty, Replacement; Bone and Bones; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Skin; Skin Pigmentation

Minocycline and a non-steroidal anti-inflammatory drug (NSAID) indomethacin, have anti-inflammatory activities and are both used in the management of rheumatoid arthritis. However, there are no reports on whether coadministration of these drugs could potentiate each other's activities in alleviating pain and weight bearing deficits during arthritis.. LPS was injected to BALB/c mice intraperitoneally (i.p.) to induce thermal hyperalgesia. The hot plate test was used to study thermal nociception in naïve BALB/c and C57BL/6 mice and BALB/c mice with LPS-induced thermal hyperalgesia and to evaluate antinociceptive effects of drugs administered i.p. Monoarthritis was induced by injection of LPS intra-articularly into the right hind (RH) limb ankle joint of C57BL/6 mice. Weight bearing changes and the effect of i.p. drug administration were analyzed in freely moving mice using the video-based CatWalk gait analysis system.. In naïve mice indomethacin (5 to 50 mg/kg) had no significant activity, minocycline (25 to 100 mg/kg) produced hyperalgesia to thermal nociception, however, coadministration of minocycline 50 mg/kg with indomethacin 5 or 10 mg/kg produced significant antinociceptive effects in the hot plate test. A selective inhibitor of COX-1, FR122047 (10 mg/kg) and a selective COX-2 inhibitor, CAY10404 (10 mg/kg) had no significant antinociceptive activities to thermal nociception in naïve mice, however, coadministration of minocycline, with CAY10404 but not FR122047 produced significant antinociceptive effects. In mice with LPS-induced hyperalgesia vehicle, indomethacin (10 mg/kg) or minocycline (50 mg/kg) did not produce significant changes, however, coadministration of minocycline plus indomethacin resulted in antinociceptive activity. LPS-induced RH limb monoarthritis resulted in weight bearing (RH/left hind (LH) limb paw pressure ratios) and RH/LH print area ratios deficits. Treatment with indomethacin (1 mg/kg) or minocycline (50 mg/kg) had no effects on the weight bearing and print area ratios deficits of monoarthritic mice. However, combination of minocycline plus indomethacin restored weight bearing and paw print area ratios of monoarthritic mice similar to that observed in non-arthritic control mice.. Coadministration of indomethacin or a selective COX-2 inhibitor, CAY10404 with minocycline potentiates their effects and results in antinociception against thermal nociception, reduction of thermal hyperalgesia and alleviation of weight bearing deficits in monoarthritic mice at doses where either drug alone has no significant activity. Thus, the coadministration of lower doses of a NSAID or a selective COX-2 inhibitor plus minocycline could be useful in the management of inflammatory pain and arthritis.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Hyperalgesia; Indomethacin; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Minocycline; Treatment Outcome

To report our experience with minocycline-induced autoimmunity (MIA) in children, with an emphasis on the potential for chronicity.. Retrospective cohort study of patients with development of rheumatologic symptoms while receiving minocycline between 1996 and 2006.. Twenty-seven children were diagnosed with MIA at a single pediatric rheumatology practice. The mean age at onset was 16.5 +/- 1.39 years. The mean duration of minocycline use before diagnosis was 13.0 +/- 10.8 months. All patients presented with constitutional symptoms. Twenty-two had polyarthralgia, and 17 had polyarthritis, mostly affecting hands and feet. On the basis of disease duration after discontinuation of minocycline, we divided subjects into 3 categories: transient, intermediate, and chronic. Seven patients had development of chronic autoimmune disease that was still active at last follow-up, a mean of 31.6 +/- 13.0 (13-48) months after onset. Six patients followed an intermediate course, with resolution of symptoms within 12 months, and 14 patients had symptoms that resolved rapidly on discontinuation of minocycline. All patients with a chronic course had evidence of arthritis at presentation.. A substantial proportion of children with MIA had development of chronic symptoms with the potential for significant morbidity. Physicians who prescribe minocycline should be aware of its propensity for inducing potentially serious autoimmune phenomena.

Topics: Adolescent; Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Antinuclear; Antibodies, Antiphospholipid; Arthritis; Autoantibodies; Autoimmune Diseases; Autoimmunity; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Humans; Male; Minocycline; Prognosis; Retrospective Studies; Time Factors

Topics: Anti-Bacterial Agents; Arthritis; Female; Humans; Hyperpigmentation; Middle Aged; Minocycline; Nails; Tongue

To determine the in vitro effects of tetracyclines and nonsteroidal antiiflammatory drugs on interleukin 1alpha (IL-1alpha) induced NO production and biosynthesis of inducible NO synthase (iNOS) by articular chondrocytes.. Bovine chondrocytes were cultured in alginate beads. Cells were treated with IL-lalpha in the presence or absence of drugs at various concentrations. Expression of mRNA for iNOS was analyzed by reverse transcription polymerase chain reaction-ELISA. Protein synthesis of iNOS was determined by immunoprecipitation. NO production was taken as a measure for the activity of the enzyme.. Minocycline dose dependently reduced IL-1 stimulated NO production by inhibition of the mRNA expression (IC50 = 69.9 microM) and protein synthesis (IC50 = 37.11 microM) of iNOS. Diclofenac-Na at a concentration of 10 microM only weakly reduced nitrite accumulation and mRNA expression of iNOS. No effects were observed for tetracycline, doxycycline, and meloxicam.. Inhibition of iNOS in articular chondrocytes may be a new mechanism by which minocycline could exert its beneficial effects in the treatment of joint diseases.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Cattle; Cell Survival; Cells, Cultured; Chondrocytes; Diclofenac; Interleukin-1; Joints; Meloxicam; Minocycline; Nitric Oxide Synthase; Thiazines; Thiazoles

To describe the clinical symptoms and serology of drug-induced lupus in patients treated with the semisynthetic tetracycline derivative, minocycline.. For a 5-year period, all consultant rheumatologists and dermatologists in the West of Scotland were asked to report any suspected cases of a lupus-like syndrome to one center. Twenty cases were identified on the basis of arthritis, positive antinuclear factor and at least one other extraarticular feature following treatment for acne with minocycline. Case histories were reviewed to determine any demographic, clinical, or serological correlations.. Minocycline had been prescribed for a mean of 25 months for the 20 patients identified with drug-induced lupus; 15 were female, 5 were male with a mean age of 24 years. All patients had arthritis and most had at least one other extraarticular feature including lethargy, myalgia, fevers, Raynaud's phenomenon, abdominal pain, and butterfly rash. None had renal involvement. All symptoms resolved at a mean of 15.7 weeks after discontinuation of minocycline treatment.. Minocycline is widely used in the treatment of acne and increasingly in the treatment of rheumatic diseases. Although the absolute risk of developing drug-induced lupus is relatively low, it has been estimated that current use of minocycline is associated with an 8.5 fold increased risk of developing a lupus-like syndrome. Prescribing physicians must be vigilant for any of the characteristic symptoms to avoid unnecessary morbidity, investigations, and therapy.

Topics: Acne Vulgaris; Adolescent; Adult; Anti-Bacterial Agents; Arthritis; Female; Humans; Lupus Erythematosus, Systemic; Male; Minocycline; Scotland; Treatment Outcome

Topics: Acne Vulgaris; Adolescent; Adult; Anti-Bacterial Agents; Arthralgia; Arthritis; Case-Control Studies; Cohort Studies; Drug Eruptions; Female; Humans; Lupus Erythematosus, Systemic; Male; Minocycline; Odds Ratio

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis; Azathioprine; Calcium Channel Blockers; Drug-Related Side Effects and Adverse Reactions; Humans; Immunosuppressive Agents; Minocycline; Mycophenolic Acid; Nifedipine; Pemphigus; Penicillamine; Skin

Prolonged treatment with minocycline for acne vulgaris has been associated with the development of arthralgia, arthritis, and other autoimmune phenomena. We characterized the clinical, laboratory, and immunological profiles of seven patients with this syndrome.. Clinically the patients were studied with special emphasis on prior minocycline treatment, presenting symptoms, physical findings, course, and outcome. Laboratory tests included fluorescent antinuclear and antineutrophil cytoplasmic (ANCA) antibodies, as well as antibodies to myeloperoxidase, bactericidal permeability increasing protein, elastase, cathepsin G, lactoferrin, cardiolipin, and histone.. All 7 patients presented with polyarthritis or arthralgia, morning stiffness, and fever after 6 to 36 months of minocycline treatment. The skin was involved in five patients (three with livedo reticularis and two with subcutaneous nodules). Two patients had chronic active hepatitis. Increased titers of perinuclear ANCA (p-ANCA) were detected in all seven patients; five patients had fluorescent antinuclear antibodies, two had antihistone autoantibodies and one had anticardiolipin antibodies. Antigenic characterization of p-ANCA disclosed antibodies to bactericidal permeability increasing protein in one patient, to elastase in three patients, and to cathepsin G in five patients. Symptoms resolved in five patients upon discontinuation of minocycline; the other two patients were treated with corticosteroids and also achieved remissions.. Minocycline-induced autoimmune syndrome is characterized by reversible polyarthralgia or arthritis, morning stiffness, fever, frequent skin involvement, occasional chronic active hepatitis, and increased titers of p-ANCA with various minor p-ANCA-related antigens.

Topics: Acne Vulgaris; Adult; Anti-Bacterial Agents; Antibodies, Anticardiolipin; Antibodies, Antineutrophil Cytoplasmic; Arthralgia; Arthritis; Autoantibodies; Autoimmune Diseases; C-Reactive Protein; Female; Humans; Male; Minocycline

Seven to 22% of patients with agammaglobulinemia develop joint manifestations consisting of septic arthritis or aseptic arthritis of unclear pathogenesis. Intravenous gammaglobulin therapy seems effective on the latter condition but is burdensome and expensive. We report the case of a patient with common variable immunodeficiency and aseptic oligoarthritis in which minocycline therapy was effective in relieving the joint symptoms.

Topics: Agammaglobulinemia; Arthritis; Common Variable Immunodeficiency; Female; Humans; Middle Aged; Minocycline

Pyoderma gangrenosum often presents a difficult therapeutic challenge. The case is described of a 42-year-old black man with the association of cystic acne, hidradenitis suppurativa, and seronegative arthritis with pyoderma gangrenosum. The pyoderma gangrenosum ulcers remained refractory to treatment until therapies aimed in part at the associated diseases were begun. Minocycline was given for treatment of cystic acne and hidradenitis suppurativa as well as pyoderma gangrenosum. Sulfasalazine was prescribed for seronegative arthritis as well as pyoderma gangrenosum. The combination therapy permitted healing of the pyoderma gangrenosum ulcers.

Topics: Acne Vulgaris; Adult; Arthritis; Cysts; Drug Therapy, Combination; Hidradenitis Suppurativa; Humans; Male; Minocycline; Pyoderma Gangrenosum; Sulfasalazine; Treatment Outcome

To describe a novel iatrogenic immunological reaction produced by minocycline.. The clinical course and laboratory results of three women who presented with similar rheumatological manifestations after a prolonged exposure to minocycline are described. All three presented a unique reaction manifested by fever, arthritis/arthralgia and livedo reticularis during treatment with minocycline for acne vulgaris. The clinical syndrome was associated with high titre of serum perinuclear anticytoplasmatic antibodies (p-ANCA) and antimyeloperoxidase antibody (anti-MPO). Symptoms resolved after stopping the drug and recurred promptly after rechallenge in all three patients.. Minocycline, which is widely used in the treatment of acne, often without adequate supervision, may induce arthritis and livedo vasculitis associated with anti-MPO.

Topics: Acne Vulgaris; Adult; Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Arthritis; Autoantibodies; Biomarkers; Female; Fever; Humans; Minocycline; Peroxidase; Skin Diseases, Vascular

Topics: Adult; Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Arthritis; Humans; Male; Minocycline

Topics: Adult; Arthritis; Female; Humans; Minocycline; Pyoderma; Skin Ulcer; Tetracyclines