minocycline and Synovitis

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that occurs two to four times as often in women as in men and increases in incidence with advancing age. It affects synovial-lined joints and can also affect the pulmonary, cardiac, nervous, integumentary, and reticuloendothelial systems. RA is manifested clinically by malaise and fatigue, followed by a symmetric pattern of joint inflammation characterized by pain and stiffness. RA most likely occurs in the setting of a genetically predisposed individual, triggered by infectious agents or endogenous antigens. Many of the newer treatments being studied involve blocking cytokine-mediated interactions between cells of the synovium.

Topics: Aged; Antibodies, Monoclonal; Arthritis, Rheumatoid; Cyclohexanes; Diphtheria Toxin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Herpesvirus 4, Human; Humans; Interferon-gamma; Interleukin 1 Receptor Antagonist Protein; Interleukin-2; Lymphocyte Activation; Male; Methotrexate; Minocycline; Neoplasm Proteins; O-(Chloroacetylcarbamoyl)fumagillol; Parvoviridae; Receptors, Tumor Necrosis Factor, Type II; Recombinant Fusion Proteins; Sesquiterpenes; Sialoglycoproteins; Synovitis; Tumor Necrosis Factor Decoy Receptors

Minocycline, a semi-synthetic tetracycline, was injected into one hind joint of twenty-two rabbits with zymosan-induced arthritis, while the contralateral joint served as a control. A local inflammatory reaction was observed a few days after the zymosan injection. Most clinical parameters such as knee diameter, systemic temperature, sedimentation rate and blood cell count did not change throughout the experiment both in control and minocycline treated rabbits. However, the zymosan platelet counts rose from 3.4x10(5)/microL to 5x10(5)/microL, as well as the level of serum fibrinogen (from 99 mg% to 370 mg%). Microscopically, a perivascular infiltrate consisting of lymphocytes and polymorphonuclear cells was seen. Lymphoid follicles as well as plasma cells epitheloid and giant cells were also observed. A mild tendency to fibrosis and lesser inflammatory reaction in the minocycline treated knees was noted. Our data suggest that intraarticular minocycline treatment did not alleviate the course of the rheumatoid-like inflammatory reaction of the knee joint.

Topics: Animals; Anti-Bacterial Agents; Injections, Intra-Articular; Knee Joint; Male; Minocycline; Rabbits; Synovial Membrane; Synovitis; Treatment Failure; Zymosan

Extracellular phospholipases A2 play an important role in articular and extra-articular inflammatory processes. Secretory non-pancreatic phospholipase A2 (PLA2) has been implicated in the pathogenesis of articular inflammation in rheumatoid arthritis, whereas pancreatic PLA2 contributes to the tissue damage associated with acute pancreatitis. Since in experimental models lipophilic tetracyclines such as minocycline and doxycycline are antiinflammatory, we examined their effects on PLA2 activity using two assay systems in vitro. We found that minocycline and to a lesser degree doxycycline were markedly inhibitory to both pancreatic and non-pancreatic PLA2. Using [14C]oleic acid labeled Escherichia coli membrane phospholipids as substrate, the IC50 values for minocycline and doxycycline were 3.6 x 10(-5) M (18 micrograms/mL) and 0.98 x 10(-4) M (47 micrograms/mL), respectively. In a scooting mode assay using the synthetic phospholipid 1-palmitoyl-2-(10-pyrenedecanoyl)-3-L-phosphatidylmethanol as substrate, IC50 values for minocycline were 5 microM (2.47 micrograms/mL) for non-pancreatic PLA2 and 8 microM (3.95 micrograms/mL) for pancreatic PLA2. Addition of excess calcium up to 50 mM did not reverse the inhibitory activity of tetracyclines. We conclude that lipophilic tetracyclines inhibit PLA2, probably by interaction with the substrate, and may be a useful adjunct in the therapy of inflammatory conditions in which PLA2 is implicated pathogenetically.

Topics: Animals; Doxycycline; Humans; Minocycline; Pancreatitis; Phospholipases A; Phospholipases A2; Recombinant Proteins; Swine; Synovial Fluid; Synovitis

A patient with systemic lupus erythematosus had a protracted skin infection with Mycobacterium marinum after a puffer fish sting. Disseminated cutaneous and synovial disease was associated with clinically active systemic lupus erythematosus two years after the initial infection. The infection was poorly responsive to multiple antituberculous regimens. Hematogenous spread of infection was the likely route of dissemination.

Topics: Adult; Animals; Cellulitis; Female; Fish Venoms; Fishes, Poisonous; Humans; Lupus Erythematosus, Systemic; Minocycline; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Skin Diseases, Infectious; Synovitis; Tendinopathy; Wrist