Comparative effects of ciprofloxacin and ceftazidime on cytokine production in patients with severe sepsis caused by gram-negative bacteria.

In the present study the effect of ciprofloxacin versus ceftazidime on concentrations of pro- and anti-inflammatory cytokines in the sera of patients with severe sepsis was evaluated. The study included 58 previously healthy patients suffering from severe sepsis caused by gram-negative bacteria, treated with either ciprofloxacin or ceftazidime after thorough clinical and microbiological evaluation and followed up for clinical outcome. Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1b (IL-1b), IL-6, and IL-8 and of the anti-inflammatory cytokine IL-10, as well as of IL-1 receptor antagonist and soluble TNF receptors I and II, in serum were measured at baseline and 24 and 48 h after the first antimicrobial dose. Mean SAPS-II scores, development of septic shock, and mortality rates were similar in the two groups (43.2 +/- 9.2, 21.4%, and 14.3% in the ceftazidime group versus 49.8 +/- 11.3, 20%, and 13.3% in the ciprofloxacin group). Serum TNF-alpha and IL-6 levels at 24 and 48 h were significantly lower in the ciprofloxacin group, while the IL-10/TNF-alpha ratio was significantly higher, than those for the ceftazidime group. Among patients with high baseline TNF-alpha levels, there were significant increases in the IL-10/TNF-alpha ratio at both 24 and 48 h over that at admission for the ciprofloxacin group, while no differences were noted in the ceftazidime group. These results indicate that ciprofloxacin may have an immunomodulatory effect on septic patients by attenuating the proinflammatory response, while there is no evidence that differences in the cytokines measured have any impact on the final outcome.

Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options.

Serum concentrations of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, and the anti-inflammatory cytokine Il-10, and IL-1 receptor antagonists (IL-1ra) and soluble TNF receptors (sTNFRs) were measured in 65 patients with severe sepsis. All patients were evaluated clinically and microbiologically and were followed up for clinical outcome. Levels of both pro- and anti-inflammatory cytokines were significantly elevated in patients with sepsis. Elevated serum IL-10 and TNF-alpha levels and a high IL-10 to TNF-alpha ratio were associated with death, whereas higher levels of TNF-alpha, IL-6, IL-1ra, and sTNFR were detected in patients with an early hemodynamic deterioration. Interleukin-10 and IL-10:TNF-alpha ratio remained higher in nonsurvivors, whereas IL-10 paralleled the sepsis score. Although both the inflammatory and anti-inflammatory response is profoundly augmented in patients with severe sepsis, the sustained overproduction of the anti-inflammatory cytokine IL-10 is the main predictor of severity and fatal outcome.