mycophenolic-acid and Pleurisy

While pleuropulmonary involvement in systemic lupus erythematosus (SLE) is a common occurrence, shrinking lung syndrome (SLS) is a rare complication of SLE, particularly in children. We report on a teenager girl with a primary SLE diagnosis, which was based upon clinical, imaging, lung-function and histological findings ascertained to be compatible with SLS. Following a pneumonia, the patient developed inflammatory residues in the lower lobes, an event that probably caused diaphragmatic immobility and subsequently led to SLS. Treatment response to steroids, cyclophosphamide and hydroxychloroquine in this case was excellent, and efficacy was more profound than previously has been reported in the literature with respect to pediatric patients. This case report argues that prognosis of SLS in SLE is likely to be favorable when the diagnosis is made early and the disease is treated appropriately.

Topics: Chest Pain; Child; Cyclophosphamide; Diaphragm; Dyspnea; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Methylprednisolone; Mycophenolic Acid; Pleurisy; Pulmonary Atelectasis; Radiography; Syndrome; Treatment Outcome

A promising therapeutic approach to reducing inflammation is to inhibit the production of proinflammatory cytokines (e.g., tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β], vascular endothelial growth factor alpha (VEGF-α), and, as shown more recently, interleukin-17 [IL-17]). In the present study, the authors have demonstrated the anti-inflammatory effects of mycophenolate mofetil (MMF) in in vivo experiments and have investigated the mechanism of action underlying those effects. Oral administration of MMF significantly inhibited leukocyte influx during the first (4 hours) and second (48 hours) phases of inflammation in a mouse model of pleurisy caused by carrageenan (P < .01). As expected, MMF suppressed protein levels of TNF-α, IL-1β, VEGF-α, and IL-17A (P < .01). This inhibitory effect was due to down-regulation of mRNA expression for these proinflammatory cytokines (P < .01). These results provide evidence of MMF-mediated inhibition of proinflammatory cytokines, and these anti-inflammatory effects are assumed to result mainly from the inhibition of the synthesis and release of TNF-α, IL-1β, VEGF-α, and IL-17A from activated leukocytes. These findings suggest that MMF might be an applicable therapeutic in the regulation of the inflammatory response-a response in which the humoral system plays a pivotal role.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cytokines; Immunosuppressive Agents; Inflammation; Interleukin-17; Interleukin-1beta; Leukocytes; Mice; Mycophenolic Acid; Pleurisy; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Herein we present a case of a patient with systemic lupus erythematosus (SLE) and a sterile empyematous pleural effusion, a complication not generally associated with SLE. A discussion of the diagnostic and treatment dilemmas follows the case presentation.

Topics: Adult; Biopsy; Diagnosis, Differential; Female; Humans; Immunosuppressive Agents; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid; Pleura; Pleural Effusion; Pleurisy

Generation of oxidative stress induced by reactive oxygen species (ROS) and nitrogen (RNS) is believed to be a primary factor in the etiology of various inflammatory diseases. Although, the process of generation of oxygen species is a physiological event, in the inflammatory process this event is increased and produces large amounts of reactive species that leads to lipid peroxidation and to cell death. Mycophenolate mofetil (MMF) is a drug effective in protecting against chronic allograft failure and recently was introduced as an alternative for the treatment of various inflammatory diseases such as glomerulopathies, systemic lupus erythematosus and systemic vasculitis. Based on studies of the anti-inflammatory effect of MMF the aim of this study was to evaluate the effects of MMF on the inhibition of leukocytes and exudation, as well as myeloperoxidase and some antioxidant enzyme activities using carrageenan-induced pleurisy in mice. Our results showed that MMF significantly decreased leukocyte influx (P<0.01), exudation (P<0.01), superoxide dismutase (P<0.05), catalase (P<0.05), glutathione peroxidase (P<0.01), glutathione S-transferase (P<0.01) activities, levels of lipid peroxidation (P<0.05), as well as myeloperoxidase activity (P<0.05) on both phases (4h and 48h) of the inflammatory response induced by carrageenan into the mice pleural cavity. In conclusion, the anti-inflammatory effect of MMF may be, at least in part, via inhibition of ROS and/or NRS overgeneration, and consequently, attenuating the related oxidative stress.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Catalase; Cell Count; Cell Movement; Dexamethasone; Disease Models, Animal; Glutathione Peroxidase; Glutathione Transferase; Indomethacin; Leukocytes; Leukocytes, Mononuclear; Lipid Peroxidation; Mice; Mice, Inbred Strains; Mycophenolic Acid; Neutrophils; Oxidative Stress; Peroxidase; Pleural Effusion; Pleurisy; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Mycophenolate mofetil 1.5 g daily (30 mg/kg body weight) was given to a patient with ankylosing spondylitis, ulcerative colitis, and severe refractory polymyositis after conventional treatment regimes had failed. No severe side effects occurred. Considerable improvement of clinical symptoms and electromyographic findings were seen within 6 months after the initiation of mycophenolate mofetil, allowing for tapering and discontinuation of methylprednisolone. Mycophenolate mofetil may be considered as an useful alternative in the treatment of polymyositis when standard therapeutic regimens fail.

Topics: Anti-Inflammatory Agents; Autoimmune Diseases; Colitis, Ulcerative; Electromyography; Female; Humans; Immunosuppressive Agents; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pleurisy; Polymyositis; Retreatment; Spondylitis, Ankylosing; Syndrome