Glucan enhances survival in an intraabdominal infection model.
The immunomodulator glucan exists in two forms, particulate (glucan-P) and soluble (glucan-F). Both preparations of glucan, either alone or in combination with antibiotic therapy, were evaluated for their ability to augment survival in rats following cecal ligation and puncture (CL/P). Adult male rats were infused once daily for 5 consecutive days with either glucan-P (10 mg/kg), glucan-F (10 mg/kg), or 5% (w/v) dextrose in water. Three days later all rats underwent CL/P. Postoperatively, the rats received (a) no therapy, (b) saline (1 ml subcutaneously every 12 hr) or (c) ampicillin (33 mg/kg subcutaneously every 12 hr) for 7 days. Without any associated pre-or postoperative treatment, CL/P was associated with an 85% 7-day mortality. Neither glucan preparation alone significantly altered this mortality. Administering ampicillin postoperatively decreased the mortality to 53% (P less than 0.001 vs untreated controls). When postoperative ampicillin therapy was combined with preoperative glucan treatment, the mortality was reduced even further (26% for glucan-P, 21% for glucan-F; P less than 0.02 vs ampicillin-treated controls). We conclude from these results that (i) neither glucan preparation alone effectively enhances survival following CL/P when using the doses and administration schedule employed herein, (ii) both glucan-P and glucan-F do act synergistically with antibiotics to enhance survival in this rat model of polymicrobial sepsis, and (iii) in this particular model, nontoxic glucan-F is as efficacious as glucan-P.
Bowers
G J
GJ
Department of Surgery, Uninformed Services University of the Health Sciences, Edward F. Hebert School of Medicine, Bethesda, Maryland 20814-4799.
Patchen
M L
ML
MacVittie
T J
TJ
Hirsch
E F
EF
Fink
M P
MP
D000005:Abdomen; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000667:Ampicillin / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001424:Bacterial Infections / Q000401:mortality / Q000517:prevention & control*; D002432:Cecum / Q000601:surgery*; D004338:Drug Combinations; D004357:Drug Synergism; D005936:Glucans / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008026:Ligation; D008297:Male; D011677:Punctures; D051381:Rats; D011919:Rats, Inbred Strains
D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D005936:Glucans; D000667:Ampicillin