Immunomodulatory effects of quinolones

Dalhoff, A.; Shalit, Itamar

doi:10.1016/s1473-3099(03)00658-3

Cited by 275 publications

(224 citation statements)

References 98 publications

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“…The exclusion criteria were: pregnancy or amenorrhea during the previous month, use of antibiotics in the previous two weeks 7,11 , previous use of oral or systemic steroids, chemotherapy, cancer, and co-infection with HIV or other immunodeficiency. Healthy subjects considered as controls were non-pregnant residents from Lima, without previous infection of B. bacilliformis, recent illnesses, or previous history of primary or secondary immunodeficiency.…”

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confidence: 99%

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study

Huarcaya

Best

Rodriguez-Tafur

et al. 2011

Rev. Inst. Med. trop. S. Paulo

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SUMMARYHuman Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre-and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4 + and CD8 + T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-g and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

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mentioning

confidence: 99%

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study

Huarcaya

Best

Rodriguez-Tafur

et al. 2011

Rev. Inst. Med. trop. S. Paulo

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“…One hypothesis is that 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 11 combination therapy offers more rapid microbial killing due to the presence of quinolones and hence shortens the exposure of the host to microbial products. Additionally, fluoroquinolones have an intrinsic immunomodulation effect that inhibits the production of certain pro-inflammatory cytokines [15][16][17][18]31]. The possible beneficial effects of fluoroquinolones on the systemic expression of cytokine response when combined with -lactam therapy in patients with PP have not been previously explored, but our results suggest that their potential anti-inflammatory and immunomodulatory effects persist when combined with -lactam.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, the modulation of the inflammatory response has emerged as a promising concept for improving the outcomes of CAP. Although it has been suggested that different antibiotic classes may have different effects on the systemic expression of cytokine production [15][16][17], information addressing this issue in PP is lacking.…”

Section: Introductionmentioning

confidence: 99%

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia

Padrones

García-Vidal

Fernández-Serrano

et al. 2010

Eur J Clin Microbiol Infect Dis

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Purpose: The aim of this study was to compare the evolution of systemic cytokine levels over time in patients with pneumococcal pneumonia treated either with ß-lactam monotherapy or with combination therapy (ß-lactam plus fluoroquinolone). Methods: Prospective observational study of hospitalized non-immunocompromised adults with PP. Concentrations of IL-6, IL-8, IL-10 and TNF-α were determined on days 0, 1, 2, 3, 5, and 7. Patients on ß-lactam monotherapy were compared with those receiving combination therapy. Results: Fifty-two patients were enrolled in the study. Concentrations of IL-6, IL-8, and IL-10 decreased rapidly in the first days after admission, in accordance with the mean time to defervescence. High levels of IL-6 were found in patients with the worst outcomes, measured by the need for intensive care unit admission and mortality. No major differences in demographic or clinical characteristics or severity of disease were found between patients treated with ß-lactam monotherapy or combination therapy. IL-6 levels fell more rapidly in patients with combination therapy in the first 48 hours (p=0.016). Conclusions: Our data suggest that systemic expression of IL-6 production in patients with PP is correlated with prognosis. Initial combination antibiotic therapy produces a faster decrease in this cytokine in the first 48 hours. We submitted you the revised manuscript entitled "Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia". We have taken into consideration all the reviewer's suggestions. Please find below a list of responses point by point to the reviewers' comments. Sincerely, Carolina Garcia-Vidal Infectious Diseases Service. Hospital Universitari de Bellvitge Feixa llarga s/n. 08907 L'Hospitalet, Barcelona, Spain E-mail: caroglv75@hotmail.com Fax: 34 93 2607637Comments to the Author:Reviewer #1: Prospective, non randomized study on the evolution and the impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia. A total of 52 patients enrolled. Data on the evolution of the systemic cytokine levels obtained every 24 hours during the first 5 days and on day 7. In 39 selected patients, the impact of B-lactam alone vs. Blactam plus fluoroquinolone on the systemic cytokine levels was assessed. Results showed that high levels of IL-6 at inclusion predicted the worst outcomes, including admission to ICU and mortality. In the group of patients treated with the combination, IL-6 levels fell more rapidly in the first 48 hours. COMMENTSThe study confirms previous reports that have shown a correlation of IL-6 levels at entry and prognosis. The results of the comparative study on the impact of antibiotic therapy showed that combination therapy was associated with a faster decrease in IL-6 in the first 24 and 48 hours of treatment. The Introduction, Methods and Results are appropriate and pertinent information is provided. In the Discussion, the authors elaborate considerably on the potential advantages of combination vs. monotherapy in C...

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“…Furthermore, quinolones prove to be not only useful antibacterial agents, but also exert immunomodulation and antitumor effects (18,19). Sparfloxacin (SPFX) is one of the fluoroquinolone antibacterials and known to inhibit the HERG channel.…”

Section: Introductionmentioning

confidence: 99%

HERG K+ channel related chemosensitivity to sparfloxacin in colon cancer cells

Zhen¹

2010

Oncol Rep

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Abstract. Potassium channels are essential for the regulation of cell proliferation. As reported, HERG protein is overexpressed in a wide range of human tumors, including colon carcinoma. The aim of this study was to investigate the effects of antibacterial agents sparfloxacin (SPFX), a blocker of HERG channel, on HERG K + channel highly expressing colon cancer cells. Expression of HERG and apoptosis correlative proteins was examined by Western blotting. The MTT assay was used to detect the cytotoxicity of drugs and drug combination in vitro. Gene transfection was used to examine the changes in herg-related chemosensitivity. Cell apoptosis was analyzed by flow cytometry. The migration and invasion capacity of tumor cells by SPFX was determined by gelatin zymography assay and Boyden chamber. The in vivo efficacy of SPFX was assessed in murine colon carcinoma C26 in BALB/c mice and human colon carcinoma HCT116 xenografts in nude mice. High expression of HERG protein was detected in colon cancer C26, HCT116 and HT-29 cells. The cell viability of the colon cancer cells was inhibited by SPFX in a dosedependent manner. SPFX induced apoptosis and inhibited migration and invasion of colon cancer HCT116 cells. The increase in apoptosis was associated with a decrease in procaspase-3 and Bcl-2 protein expression. Study with hergtransfected HEK293 cells and siRNA-knock down HCT116 cells confirmed that the cell viability inhibition by SPFX was correlated with HERG expression. When combined with 5-fluorouracil, SPFX showed synergistic anti-proliferation activity in HCT116 and HT-29 cells. Furthermore, SPFX inhibited the growth of human colon carcinoma HCT116 xenografts and showed synergistic effect with 5-fluorouracil in vivo. Our finding suggested that SPFX could be a biochemical modulator in treatment of colon cancer with chemotherapeutic drugs.

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Immunomodulatory effects of quinolones

Cited by 275 publications

References 98 publications

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia

HERG K+ channel related chemosensitivity to sparfloxacin in colon cancer cells

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