Recombinant Human Granulocyte Colony-Stimulating Factor and Pseudomonas Burn Wound Sepsis

Mooney, David P.; Gamelli, Richard L.; O'Reilly, Michael; Hebert, James C.

doi:10.1001/archsurg.1988.01400350067010

Cited by 63 publications

(17 citation statements)

References 31 publications

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“…Our results confirm and extend previous studies in which pretreatment with supraphysiological doses of exogenous G-CSF provided nonspecific protection against bacterial infection. These include rodent models of P. aeruginosa (19,20), K. pneumoniae (21), and S. pneumoniae (22) infection and polymicrobial sepsis after cecal ligation and puncture (23). However, the present model significantly demonstrates that endogenous production of G-CSF can induce this protective effect, and it highlights the physiological importance of this cytokine as part of the acute phase response.…”

Section: Discussionmentioning

confidence: 68%

Production of Granulocyte Colony-Stimulating Factor in the Nonspecific Acute Phase Response Enhances Host Resistance to Bacterial Infection

Noursadeghi

Bickerstaff

Herbert

et al. 2002

The Journal of Immunology

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Mice mounting an acute phase response, induced by sterile inflammation after a single s.c. injection of casein 24 h beforehand, were remarkably protected against lethal infection with Gram-positive or Gram-negative bacteria. This was associated with enhanced early clearance of bacteremia, greater phagocytosis and oxidative burst responses by neutrophils, and enhanced recruitment of neutrophils into tissues compared with control, nonacute phase mice. Casein-induced inflammation was also associated with increased concentrations of G-CSF in serum, and administration of neutralizing Ab to this cytokine completely abrogated protection against Escherichia coli infection after casein pretreatment. Injection of recombinant murine G-CSF between 3 and 24 h before infection conferred the same protection as casein injection. In contrast, the casein-induced acute phase response affected neither serum values of TNF-α, IL-1β, or IL-6 after E. coli infection nor susceptibility to LPS toxicity. Furthermore, protection against infection was unaffected in IL-1R knockout mice, which have deficient acute phase plasma protein responses, or after nonspecific inhibition of acute phase protein synthesis by d-galactosamine or specific depletion of complement C3 by cobra venom factor. Increased production of G-CSF in the acute phase response is thus a key physiological component of host defense, and pretreatment with G-CSF to prevent bacterial infection in at-risk patients now merits further study, especially in view of increasing bacterial resistance to antibiotics.

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Section: Discussionmentioning

confidence: 68%

Production of Granulocyte Colony-Stimulating Factor in the Nonspecific Acute Phase Response Enhances Host Resistance to Bacterial Infection

Noursadeghi

Bickerstaff

Herbert

et al. 2002

The Journal of Immunology

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“…Compared with control treatment, G-CSF at a low dose (15 ,ug/kg/day) had no activity in spleen or lungs, but in association with clarithromycin, it was more effective than clarithromycin alone in both organs, except in spleen at day Log 15: in spleen, P = 0.32 at day 15 and P < 0.05 at day 21; in lungs, P = 0.02 at day 15 and P = 0.015 at day 21. The high-dose regimen of G-CSF (300 ,ug/kg/day) alone or combined with clarithromycin (data not shown) was no more effective than the low-dose regimen.…”

Section: Resultsmentioning

confidence: 94%

Efficacy of granulocyte colony-stimulating factor and RU-40555 in combination with clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice

Lazard

Perronne

Cohen

et al. 1993

Antimicrob Agents Chemother

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We compared the activities of two different biological-response modifiers with that of clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice. Mice were pretreated daily with clarithromycin (50 mg/kg of body weight subcutaneously [s.c.]), RU-40555 (100 mg/kg s.c.), or granulocyte colony-stimulating factor (G-CSF) at low dose (15 micrograms/kg intraperitoneally [i.p.]) or high dose (300 micrograms/kg i.p.) 3 days before intravenous challenge with 2.5 x 10(7) CFU of the MO-1 strain of M. avium complex. Mice were treated daily until sacrifice at day 1, 8, 15, or 21 after challenge, and the numbers of CFU were measured per gram of tissue in lung and spleen. Compared at day 21 with control treatment, clarithromycin significantly decreased the level of infection in spleen (P < 0.0001) and lungs (P < 0.0001). Compared with control treatment, G-CSF at low dose had no activity, but G-CSF in combination with clarithromycin was more effective than clarithromycin alone in spleen (P < 0.05) and lungs (P < 0.015). The high dose of G-CSF was as effective as the low dose. RU-40555 alone had no beneficial activity. The RU-40555-clarithromycin combination was more effective than control treatment in spleen (P = 0.0001) and lungs (P < 0.0005) and more effective than clarithromycin alone in spleen (P < 0.009) but not in lungs. Thus, our experiments suggest that clarithromycin alone or in combination with G-CSF should be further evaluated for the prophylaxis of M. avium complex infection.

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“…It also induces endothelial cell proliferation and migration (Bussolino et al 1991). In an animal model of burns and infection, G-CSF treatment was found to increase chemotaxis (Mooney et al 1988). It can be speculated that G-CSF augments the recruitment in vivo by effectively lowering the threshold for the chemotactic signals necessary to initiate directed neutrophils consistency to the wound site because it is known that G-CSF enhances the binding of polymorphonuclear leukocytes' (PMN) to chemotactic peptides in vitro (Cohen et al 1988).…”

Section: Resultsmentioning

confidence: 99%

Effects of Granulocyte-Colony Stimulating Factor on Wound Healing in a Mouse Model of Burn Trauma

Eroğlu

Agalar

Altuntaş

et al. 2004

Tohoku J. Exp. Med.

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The effects of burn trauma and granulocyte-colony stimulating factor (G-CSF) treatment on wound healing in a surgical incision model were studied. Sixty adult male mice were used in this study. Under general anesthesia hot water at 97°C was applied for 3 sec to the dorsum of the mice in order to achieve 20% burn wound. After burn trauma, full thickness midline skin incision 2 cm in length was performed on the abdominal wall and then were sutured primarily with 4/0 polypropylene. In Group I only skin incision was performed, group II had skin incision and burn, in group III G-CSF (0.03 BU/30 g) was applied intraperitoneally after burn and skin incision. Breaking strength and 5-hydroxyproline (5-HP) levels of the wounds were calculated 5 and 10 days after the procedure. 5-HP levels and breaking strength values showed statistical difference between groups II-III and I-II (p<0.05). 5-HP levels were lowest in incision and burn group (41.80 μ g/mg). Breaking strength levels were also lowest in the same group (0.12 kg) (p<0.05). These results suggest that third degree burn causes a significant impairment on incisional wound healing and G-CSF ameliorates this impairment.burn; wound; wound healing; G-CSF

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Recombinant Human Granulocyte Colony-Stimulating Factor and Pseudomonas Burn Wound Sepsis

Cited by 63 publications

References 31 publications

Production of Granulocyte Colony-Stimulating Factor in the Nonspecific Acute Phase Response Enhances Host Resistance to Bacterial Infection

Production of Granulocyte Colony-Stimulating Factor in the Nonspecific Acute Phase Response Enhances Host Resistance to Bacterial Infection

Efficacy of granulocyte colony-stimulating factor and RU-40555 in combination with clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice

Effects of Granulocyte-Colony Stimulating Factor on Wound Healing in a Mouse Model of Burn Trauma

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