Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tuberculostatic agent isoniazid has been implicated in inducing various idiosyncratic reactions including drug-induced lupus. The mechanism is unknown but may involve a reactive metabolite of the drug. Isoniazid was oxidized by activated leukocytes to isonicotinic acid. Myeloperoxidase is likely the enzyme in the leukocyte involved, since the oxidation was inhibited by azide, which inhibits myeloperoxidase, and by catalase, which catalyzes the breakdown of hydrogen peroxide. The same metabolic profile was observed when isoniazid was incubated with purified myeloperoxidase and hydrogen peroxide. The rate of the reaction was increased in the presence of chloride. Hypochlorous acid was also able to oxidize isoniazid to isonicotinic acid. Isoniazid, or an oxidative product, inhibited the reaction when high initial substrate concentrations were used. Isoniazid is oxidized by activated leukocytes, possibly to a reactive intermediate, which may have implications for isoniazid-induced lupus.
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PMID:Metabolism of isoniazid by activated leukocytes. Possible role in drug-induced lupus. 135 11

A case of lupus-vulgaris-like infection caused by Mycobacterium xenopi in a 62-year-old immunocompetent female patient is presented. A large cutaneous infiltration was seen in the right periorbital region. Histological examination revealed a granulomatous reaction of epithelioid cells and giant cells. M. xenopi was isolated from biopsy material and tuberculosis could be excluded. Isoniazid was effective in healing the lesion within a year. Such infections are well known for other mycobacteria but to our knowledge had not yet been described for M. xenopi. The characteristics of human infections with M. xenopi are summarized in a review of the literature and criteria for the diagnosis of atypical cutaneous mycobacterioses are proposed.
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PMID:[A lupus-vulgaris like atypical mycobacteriosis caused by Mycobacterium xenopi (lupus xenopi)]. 139 3

Isoniazid, a tuberculostatic agent, induced in some patients lupus-like syndrome. Pathomechanism of this autoimmune phenomenon is unknown, and it is suggested that is associated with disturbances in immunoregulatory processes. Human peripheral blood mononuclear cells or T cells were isolated from healthy donors and were stimulated with phytohemagglutinin or antibody against CD3 cell receptor antigen. Proliferation, measured as thymidine uptake, was determined in in vitro cultures of the cells. Isoniazid added to cell cultures decreased proliferation at higher doses, and produced a slight increase in proliferation in concentration 10(-5)-10(-6) M. Isoniazid alone has no mitogenic activity. The viability of the cells, determined as the Trypan blue exclusion test, was decreased only at the presence of the highest used dose of isoniazid (10(-2) M), thus the results were not influenced by the toxic effects of the drug.
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PMID:Studies on immunomodulatory properties of isoniazid. I. Effect of isoniazid on mitogen- and anti-CD3 antibody-induced proliferation of human peripheral blood mononuclear cells and T cells. 214 Oct 35

Isoniazid (INH) is one among many drugs capable of inducing autoantibodies and, in some cases, a lupus-like syndrome (LE). A longitudinal study was performed in 24 tuberculosis patients treated with INH to detect antibodies (A-AH) to total histones and fractions. Antinuclear antibodies were observed in two patients after treatment. Higher frequency of IgM-AH was also observed. IgM-AH binding to all fractions were observed in those serum samples exhibiting stronger ELISA reactivity. Conversely, binding to only H1 occurred when lower IgM-AH activity was tested. Correlations with clinical expressions of LE were not observed in the present study.
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PMID:[Clinical and biochemical characterization of isoniazid-induced auto-antibodies]. 225 21

Isoniazid (INH) and hydralazine (HYD) are transglutaminase (TGase, E.C.2.3.2.13.) substrates containing catalytically recruitable hydrazyl groups. Since they can be expected to inhibit TGase-mediated cell functions by competing with physiological substrates, their effect upon allogeneically and lectin-induced proliferation of mononucleocytes and upon zymosan-induced chemiluminescence of phagocytes was studied. Both compounds inhibited chemiluminescence in a dose-dependent manner. ID50 of HYD was consistently below 20 microM, while that of INH was above 120 microM. Proliferation of immunocompetent cells was suppressed by HYD with an ID50 of 60 microM, INH was inhibitory only above 5000 microM. Analogs of both compounds not containing hydrazyl groups proved to be inactive. Control experiments indicated that inhibition is not due to toxicity or lipophilicity of the compounds, structural analogs lacking a hydrazyl moiety were inactive. It is suggested that, in vivo, HYD interferes with signal-induced TGase-dependent leucocyte functions essential for immunologic stability, and that the resultant dysregulation with disruption of self tolerance contributes to the HYD promoted lupus-like syndrome.
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PMID:Effects of hydrazyl group containing drugs on leucocyte functions: an immunoregulatory model for the hydralazine-induced lupus-like syndrome. 286 61

Five drugs associated with systemic lupus erythematosus were studied for their effect on the salt-induced right-handed (B) to left-handed (Z) transition of poly(dG-me5dC) X poly(dG-me5dC). Using circular dichroism spectroscopy, procainamide and hydralazine were found to reduce the midpoint of B to Z transition from 0.8M NaCl to 0.5M NaCl and to increase the rate of this transition at 1M NaCl. Isoniazid and D-penicillamine had less effect on the midpoint of transition and practically no effect on the kinetics. N-acetyl procainamide (a structurally related control for procainamide) and L-canavanine had no effect. Procainamide caused slight reduction in the helix-coil transition (melting) temperature of calf thymus DNA. At a concentration of 1:1 (DNA phosphate:drug ratio), procainamide and hydralazine also caused the aggregation of calf thymus DNA. Since altered DNA conformations, such as Z-DNA, are more immunogenic, these results suggest that the induction or stabilization of Z-DNA by these drugs might be important in the pathogenesis of at least some cases of systemic lupus erythematosus.
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PMID:Effects of lupus-inducing drugs on the B to Z transition of synthetic DNA. 371 55

Isoniazid (INH), antituberculous drug with immunomodulatory properties, have been described as lupus-like syndrome inducer. The development of autoimmunological phenomena results from immunoregulatory disturbances. The goal of this work was to determine the influence of INH on selected parameters of the immune response in vivo and in vitro. In vivo (in B6AF1 mice) the influence of long-term treatment on primary humoral response and cellular response was evaluated. Drug dose was 25 mg/kg. In vitro (using peripheral blood of volunteers) the influence of INH on mitogen induced proliferation, metabolic activity of granulocytes and production of angiogenic cytokines by diverse subpopulation of mononuclear cells was examined. The concentrations tested were 0.5 mg/ml, 5 mg/ml and 50 mg/ml. No effect of INH could be demonstrated on the production anti-SRBC antibodies nor on the cellular response in mice. In vitro INH added to the cell cultures increased PHA and ConA stimulated proliferation. The chemiluminescence of human granulocytes increased in the presence of INH. Drug enhanced production of angiogenic cytokines by human lymphocytes CD4+ and suppressed angiogenic activity of CD8+ cells. The results suggest that INH has strong immunomodulatory properties which may explain its involvement in pathogenesis of lupus-like disease.
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PMID:[Influence of isoniazid on selected parameters of immunological response]. 1076 48

An estimated incidence of drug-induced lupus erythematosus caused by all drugs is 15,000 to 20,000 cases a year, and represents approximately 5 to 10% of the total number of patients with systemic lupus erythematosus. Approximately 22% of the patients treated with isoniazid for a mean of 6 months develop antinuclear antibodies. Isoniazid-induced lupus erythematosus affects either sex equally and the most common presenting feature is arthralgia or arthritis with anemia. Fever and pleuritis occur in approximately half of the cases, and pericarditis in approximately 30% of cases. IgG antibody to the (H2A-H2B)-DNA complex appears specific for the isoniazid-induced lupus erythematosus. The drug-induced lupus presenting with cardiac tamponade is a recognized feature of many drugs such as hydralazine, procainamide, and sulfasalazine. Reported here is a case of isoniazid-induced lupus erythematosus presenting with cardiac tamponade. A 73-year-old man was treated with isoniazid for 8 months at a dose of 300 mg a day. The patient responded to the withdrawal of the isoniazid therapy and placement of a pericardial window. The existing literature on the subject is reviewed.
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PMID:Isoniazid-induced lupus erythematosus presenting with cardiac tamponade. 1189 31

A 75-year-female with a history of Isoniazid (INH) therapy for latent tuberculosis, was admitted with a 4-week duration of dyspnea, cough, and pleuritic chest pain. She was treated with intravenous antibiotics for a diagnosis of pneumonia. Her stay was complicated by development of recurrent, exudative eosinophilic pleural effusions (EPEs). When symptoms continued to worsen and she developed joint pain and anasarca and did not respond to the antibiotics, a rheumatologic work-up was performed. She was found to have positive anti-double stranded-DNA antibodies and anti-histone antibodies; thus, a diagnosis of drug-induced lupus, secondary to INH, was made. INH was discontinued, and the patient was started on prednisone; within weeks her symptoms resolved. This case illustrates a unique side effect of INH that caused exudative EPEs and drug-induced lupus with positive anti-dsDNA.
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PMID:Isoniazid (INH)-induced eosinophilic exudative pleural effusion and lupus erythematosus. A clinical reminder of drug side effects. 2203 99

Drug-induced muscle disorders are now well known and vary from a simple isolated increase in muscle enzymes to severe drug-induced myopathy. The list of drugs inducing myopathy is very long and continues to grow. The onset of muscle disorders under isoniazid often falls within a drug-induced neuropathy or a drug-induced lupus. However, the occurrence of isolated isoniazid-induced drug myopathy without neuropathy is an extremely rare condition especially with non-toxic doses. The authors report the case of a 28-year-old man, without a previous medical history, hospitalized for pulmonary tuberculosis. After initiating tuberculosis treatment for five days, he presented muscle pain, fasciculation and weakness initially involving the lower left limb that quickly propagated to all four limbs. The physical examination noted a left ankle flush, a swollen left calf and fasciculation of both calves while the neurological examination was normal. The CPK was normal. Electromyography confirmed the myopathy without neuropathic findings. Isoniazid withdrawal was marked by the rapid disappearance of the symptoms. The reintroduction of a half-dose of isoniazid only induced a few transitional muscular fasciculations. The onset of the symptoms under tuberculosis treatment, the absence of later muscle disorders, the absence of any other cause of myopathy and the total disappearance of the symptoms after isoniazid withdrawal confirmed the diagnosis of isoniazid-induced myopathy.
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PMID:[Isoniazid-induced myopathy]. 2213 79


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