Treatment of experimental gram-negative and gram-positive bacterial sepsis with the hematoregulatory peptide SK&F 107647.
SK&F 107647, a novel synthetic low-molecular-weight peptide, has demonstrated potent antiinfective activities in murine models of fungal and viral infection. To determine if the hematoregulatory activities of SK&F 107647 could offer protection over conventional antibiotic therapy or as a single agent in animal models of bacterial sepsis, rats were implanted intraperitoneally with a live bacteria-containing fibrin-thrombin clot. Rats pretreated subcutaneously or orally with SK&F 107647 and then infected with either a gram-negative (Escherichia coli) or a gram-positive (Staphylococcus aureus) bacteria-containing clot demonstrated significantly improved survival over control formulation-treated animals. Treated animals showed increased effector cell activation, measured by CD11b expression on neutrophils and monocytes, and up to 1000-fold reduction in the number of E. coli recovered from blood. Thus, the hematoregulatory activities of SK&F 107647 can increase natural host resistance to infections caused by both gram-negative and gram-positive bacteria.
DeMarsh
P L
PL
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Wells
G I
GI
Lewandowski
T F
TF
Frey
C L
CL
Bhatnagar
P K
PK
Ostovic
E J
EJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D018845:CD11 Antigens / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D005839:Gentamicins / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D018845:CD11 Antigens; D005839:Gentamicins; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C086049:SK&F 107647