Effect of antituberculous drugs on human polymorphonuclear leukocyte functions in vitro

Okuyan, Betül; İzzettin, Fikret; Sancar, Mesut; Ertaş, Özgür; Çevikbaş, Adile; Gürer, Ümran Soyoğul

doi:10.1016/j.intimp.2005.03.002

Cited by 8 publications

(11 citation statements)

References 26 publications

(27 reference statements)

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“…Many studies have examined the effects of antibiotics on the function of PMNs [13,14,15,16], but few have reported on the gene expression of PMN-activating cytokines and their receptors [17]. Both erythromycin and rifampicin have good intracellular distribution properties and may exert immunomodulatory effects.…”

Section: Introductionmentioning

confidence: 99%

Effects of Erythromycin and Rifampicin on Immunomodulatory Gene Expression and Cellular Function in Human Polymorphonuclear Leukocytes

Ubagai

Kikuchi-Ueda

et al. 2013

Chemotherapy

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Background: We investigated the effects of two antibiotics, erythromycin and rifampicin, on the immunomodulatory gene expression and cellular function of human polymorphonuclear leukocytes (PMNs). Methods: We used real-time quantitative PCR to examine the expression of immunomodulatory genes. The production of reactive oxygen species (ROS) was determined by fluorescence-activated cell sorting. PMN chemotaxis was analyzed using a KK chemotaxis chamber. Results: Stimulation of PMNs with lipopolysaccharide (LPS) resulted in increases in the mRNA levels of immunomodulatory genes. Rifampicin significantly inhibited the overexpression of TLR2, TLR4, CD14 and IL8Rs. However, erythromycin suppressed only the upregulation of TLR2 and TNFA. Neither antibiotic had an effect on the production of ROS. Rifampicin significantly inhibited PMN chemotaxis, but erythromycin had no effect. Conclusions: Erythromycin and rifampicin may play anti-inflammatory roles by affecting the expression levels of immunomodulatory genes or the chemotaxis of PMNs.

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Section: Introductionmentioning

confidence: 99%

Effects of Erythromycin and Rifampicin on Immunomodulatory Gene Expression and Cellular Function in Human Polymorphonuclear Leukocytes

Ubagai

Kikuchi-Ueda

et al. 2013

Chemotherapy

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“…Antibiotics have various side effects, and some of them may influence the functions of neutrophils [6]. Free radical reactions have been suggested to be involved in the toxic effects of several antibiotics [7][8][9][10][11]. Idiosyncratic aplastic anaemia can occur in predisposed patients after chloramphenicol, irrespective of the dosage.…”

mentioning

confidence: 99%

Chloramphenicol‐Induced Oxidative Stress in Human Neutrophils

Páez

Becerra

Albesa

2008

Basic Clin Pharma Tox

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The aim of this study was to evaluate the in vitro effect of chloramphenicol in order to determine its potential toxic effects on human neutrophils, by using assays of reactive oxygen species (ROS) determination, nitrite measurement and antioxidant systems. Chloramphenicol enabled the oxidative stress response of neutrophils and increased the ROS production at 2, 4, 8 and 16 μ g/ml, while ROS generation decreased at high concentrations (32 μ g/ml). The nitroblue tetrazolium assay shows that neutrophils incubated with chloramphenicol increased the intracellular ROS, with the extracellular production rising with a corresponding increase in antibiotic concentration. Enzymatic activities -superoxide dismutase, catalase and diaphorase enzymes -increased after chloramphenicol treatment, while the glutathione level decreased in neutrophils incubated with antibiotic. The results obtained in the present work suggest that the study of susceptibility to oxidative stress in neutrophils before chloramphenicol treatment could be adequate for in vitro toxicity screening.Oxidative stress has been associated with hepatic and renal toxicity [1], but leucocytes can also be affected in the reactive oxygen species (ROS) production by toxic substances [2]. The regulation of ROS production is particularly important in neutrophils, because these cells perform an important function in host defence against bacterial infections by producing ROS and nitrogen species, hydrolytic and proteolytic enzymes, and antimicrobial polypeptides. Although neutrophils also produce nitric oxide, the levels are low and likely to result from the activity of a constitutive nitric oxide synthase [3]. Deregulation of nitric oxide and increased oxidative and nitrosative stress are implicated in tissue damage [4].Several chemical agents can alter the cellular functions associated with the oxidative metabolism, thereby stimulating ROS production in neutrophils [5]. Antibiotics have various side effects, and some of them may influence the functions of neutrophils [6]. Free radical reactions have been suggested to be involved in the toxic effects of several antibiotics [7][8][9][10][11]. Idiosyncratic aplastic anaemia can occur in predisposed patients after chloramphenicol, irrespective of the dosage. This is thought to be due to the production by the gut flora of a nitro-reduction derivative of chloramphenicol. This derivative can induce DNA damage in replicating haematopoietic stem cells, resulting in marrow hypocellularity and progressive pancytopaenia [12]. The most common presentation, however, is a reversible, dose-dependent bone marrow suppression, which usually occurs when serum chloramphenicol levels exceed 25 mg/l for prolonged periods of time. This condition is associated with the inhibition of mitochondrial protein synthesis, and is characterized by mild marrow hypocellularity, anaemia, neutropaenia and thrombocytopaenia [13]. As non-idiosyncratic aplastic anaemia and 'grey baby' syndrome are dose-dependent complications of chloramphenicol us...

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“…In these studies, the primary goal was to investigate and compare PMN function in different groups. The results of these studies have been conflicting [8,12,13,14]. This may be due to technical differences and to different aspects of PMN function examined in the different studies.…”

Section: Resultsmentioning

confidence: 99%

“…The results of these studies have been conflicting. Some report no effect of rifampicin on PMN functions [8,18,19] while most studies report an inhibitory effect of rifampicin [20,21,22,23,24]. In the study of Duncker and Ullmann [20], the inhibitory effect was only seen at high concentrations.…”

Section: Resultsmentioning

confidence: 99%

“…For each drug and for the combination of drugs, PMNs (60 µl) from 8 different donors were incubated with subtherapeutic, therapeutic [6,7,8] and supratherapeutic concentrations of the drugs (20 µl) as described above for 30 min at 37°C in a temperature-controlled shaker before being tested for phagocytosis and oxidative burst capacity. PMNs incubated in DPBS-GACM without drugs were used as control cells.…”

Section: Methodsmentioning

confidence: 99%

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Anti-Tuberculosis Drugs and Human Polymorphonuclear Leukocyte Functions

Kielland

Vage²,

Eide³

et al. 2011

Chemotherapy

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Background: The polymorphonuclear leukocyte (PMN) is considered to be of importance in the early stages of human tuberculosis (TB). We examined the four drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) commonly used in the DOTS (directly observed treatment, short-course) strategy against TB for their effects on the functions of the human PMN, separately and combined. Methods: PMNs were incubated with subtherapeutic, therapeutic and supratherapeutic concentrations of the drugs before being tested for phagocytosis and oxidative burst capacity with Staphylococcus aureus opsonized with pooled human serum as stimuli. Flow cytometric techniques were used to compare PMN phagocytosis and oxidative burst with and without incubation in different concentrations of the drugs. Results: None of the drugs influenced PMN phagocytosis as measured by flow cytometry. Oxidative burst was attenuated only with the highest (and supratherapeutic) concentrations of isoniazid and of the combined drugs as compared to lower concentrations. Conclusions: This suggests that any deterioration in PMN function observed in TB is probably associated with the disease per se and not with the anti-TB treatment.

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Effect of antituberculous drugs on human polymorphonuclear leukocyte functions in vitro

Cited by 8 publications

References 26 publications

Effects of Erythromycin and Rifampicin on Immunomodulatory Gene Expression and Cellular Function in Human Polymorphonuclear Leukocytes

Effects of Erythromycin and Rifampicin on Immunomodulatory Gene Expression and Cellular Function in Human Polymorphonuclear Leukocytes

Chloramphenicol‐Induced Oxidative Stress in Human Neutrophils

Anti-Tuberculosis Drugs and Human Polymorphonuclear Leukocyte Functions

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