Cerebrospinal fluid of patients administered moxifloxacin modulates the secretion of cytokines from human monocytes.
To evaluate the ex vivo immunomodulatory properties of moxifloxacin, we applied serum and cerebrospinal fluid (CSF) samples from 50 patients who received a single oral dose of 400 mg. Patients were divided into 5 groups according to time lapsing between sampling and drug intake: group I, 0.5 to 1 h; group II, 1 to 2 h; group III, 2 to 4 h; group IV, 4 to 6 h; and group V, 6 to 8 h. Samples were added to cultures of U937 monocytes stimulated by 10 ng/mL of lipopolysaccharide (LPS) and 1 x 10(5) colony-forming unit (CFU) of 1 heat-killed penicillin-resistant isolate of Streptococcus pneumoniae. Concentrations of cytokines were estimated in supernatants. Concentrations of interleukin (IL)-1beta, IL-10, and IL-12 released after stimulation by LPS were significantly decreased by CSF of groups I, IV, and V. After stimulation by the heat-killed isolate, concentrations of tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6, and IL-10 were increased in the presence of CSF of group III; those of IL-12p70 were decreased by CSF of groups I and II. Concentrations of IL-1beta, IL-6, and IL-8 drawn after stimulation by LPS were significantly decreased upon addition of serum from all groups. After stimulation by the heat-killed isolate, concentrations of TNF-alpha were decreased by serum drawn from all patients; IL-1beta was increased after addition of serum of groups I, II, and V. It is concluded that CSF and serum of patients administered moxifloxacin may effectively modulate the production of pro- and anti-inflammatory cytokines by human monocytes. These results render new perspectives for the therapy for meningitis.
Giamarellos-Bourboulis
Evangelos J
EJ
4th Department of Internal Medicine, University of Athens, Medical School, 12462 Athens, Greece. giamarel@ath.forthnet.gr
Douzinas
Emmanouel E
EE
Tsaganos
Thomas
T
Pagoulatou
Alexandra
A
Livaditi
Olga
O
Vafiadou
Marianthi
M
Kanellakopoulou
Kyriaki
K
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D024841:Fluoroquinolones; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007114:Immunization; D007155:Immunologic Factors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D000077266:Moxifloxacin; D011446:Prospective Studies; D011804:Quinolines / Q000494:pharmacology*; D044967:Serum / Q000378:metabolism; D013296:Streptococcus pneumoniae; D020298:U937 Cells
D000890:Anti-Infective Agents; D001372:Aza Compounds; D016207:Cytokines; D024841:Fluoroquinolones; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D011804:Quinolines; D000077266:Moxifloxacin