Effect of ciprofloxacin on lethal and sublethal challenge with endotoxin and on early cytokine responses in a murine in vivo model

Abstract

The influence of ciprofloxacin on immune responses has been suggested by results of in vitro and in vivo studies. This effect was studied using a murine model that measured mortality and early cytokine responses after challenge with endotoxin. C57/BL6 mice weighing between 18 and 21 g were given a single intraperitoneal dose of lipopolysaccharide (LPS), ranging from 200 to 1000 microg. Mice were pre-treated with an intraperitoneal injection of 5% dextrose in sterile water containing 0.0-6.0 mg of ciprofloxacin 1 h before LPS challenge. Cytokine responses were assessed by measuring concentrations in serum separated from blood obtained by cardiac puncture of anaesthetized mice at 0, 1, 3, 6 and 24 h following LPS administration. Mice were observed for 72 h following administration of LPS and serum cytokines were measured using ELISA. More than 4.5 mg of ciprofloxacin (675-900 mg/m(2) or 225-300 mg/kg) given 1 h before LPS challenge consistently protected mice from a lethal dose of LPS (14/14 versus 0/7, P < 0.00001). Ciprofloxacin significantly attenuated the production of tumour necrosis factor-alpha and interleukin-12 response after LPS challenge. In addition, ciprofloxacin significantly increased serum interleukin-10 concentrations but had little or no effect on interleukin-6 or interleukin-1beta serum concentrations. Similar effects were evident with sublethal doses of LPS and were most pronounced at the lowest dose of LPS studied. These observations indicate that ciprofloxacin can prevent endotoxin-mediated death and alter early host cytokine responses. This effect may influence the course of infection in a manner that is independent of the drug's antimicrobial activity.

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

“…Moreover, by conjugating CpG to NPs, we could use a low dose of CpG to potently activate DCs in the LNs without substantially raising blood levels of the inflammatory cytokines TNF-α, IL-12p70, and IL-6 (Fig. S2); thus, the low dose of CpG used on the NP appears to limit toxicity that would be associated with higher doses of free CpG (9,35). Vaccination with NP-CpG-B and NP-OVA increased the proportion of CD8 + T cells capable of degranulating and secreting IFN-γ compared with vaccination with soluble CpG-B and NP-OVA.…”

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

“…TNF-␣ levels peaked 1 h after LPS injection and ranged from 100 pg/ml (22) to 600 pg/ml (1) to 15,000 pg/ml (14). Reported serum IL-6 levels peaked between 2 and 4 h after LPS injection and ranged from 900 pg/ml (1) to 5,000 pg/ml (14) to 40,000 pg/ml (24). In a murine model of sepsis caused by P. aeruginosa pneumonia, serum IL-6 levels above 3,600 pg/ml were associated with 100% mortality, whereas levels below 1,200 pg/ml were associated with 100% survival (9).…”

“…Depending on the mouse strain, the source of endotoxin, and the cytokine assays used, considerable variations in the cytokine response were reported (1,14,22,24). TNF-␣ levels peaked 1 h after LPS injection and ranged from 100 pg/ml (22) to 600 pg/ml (1) to 15,000 pg/ml (14).…”

Role of Interleukin 10 during Persistent Infection with the Relapsing Fever Spirochete Borrelia turicatae

“…The mice with the highest spirochetemia, Bt2-infected Rag1 Ϫ/Ϫ mice, had ϳ10 times more plasma IL-10 than any of the other cytokines/ chemokines, reaching levels similar to wild-type C57BL/6J mice injected with a lethal dose of lipopolysaccharide. 24 Bt2-infected Rag1 Ϫ/Ϫ mice became moribund after several weeks of persistent infection, an indication that the ability of IL-10 to protect the host from the infection is temporary. This is similar to infection with Yersinia pestis, in which IL-10 induced via toll-like receptor 2 is protective but the mice eventually reach lethal pathogen numbers.…”