Preventive effect of several drugs against Pseudomonas aeruginosa infection and the toxicity of combined tumor necrosis factor with lipopolysaccharide: relationship between lethality and the arachidonic cascade.
The participation of tumor necrosis factor (TNF) and lipopolysaccharide (LPS) in Pseudomonas aeruginosa (Pa) infection was examined. The lethal challenge of Pa or TNF and LPS injection could be prevented by pretreatment with anti-TNF antibody, polymyxin B, ONO 1078, or Shosaiko-to. The combined effects of TNF and LPS may be deeply related to the lethality of Pa infection. The activities of leukotriene(LT) C4/D4/E4 or platelet activating factor (PAF) were also related to the lethality of Pa infection, probably due to the subsequently produced TNF which acts in combination with LPS. Activating the host defence mechanism with biological response modifiers like Chinese medicines was effective against Pa infection. One mechanism could involve an activity as an LT inhibitor or PAF antagonist. Following the administration of TNF and/or LPS, the serum levels of arachidonic cascade products underwent various changes. With a combination of TNF and LPS, there was a synergistic increment of prostaglandins, thromboxane, and LT. Following pretreatment with Shosaiko-to, suppression of LTs was dominant even with the combination of TNF and LPS, which might be related to the lethality of the infection or combined TNF with LPS.
Satomi
N
N
Department of Internal Medicine, University of Tokyo, Japan.
Sakurai
A
A
Iimura
F
F
Haranaka
R
R
Haranaka
K
K
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000906:Antibodies / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000633:toxicity*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D002513:Cephamycins / Q000627:therapeutic use; D002867:Chromones / Q000627:therapeutic use; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D005260:Female; D020024:Leukotriene Antagonists; D017999:Leukotriene E4; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011112:Polymyxin B / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000097:blood / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000633:toxicity; D013189:SRS-A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000906:Antibodies; D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D002513:Cephamycins; D002867:Chromones; D004365:Drugs, Chinese Herbal; D020024:Leukotriene Antagonists; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D013189:SRS-A; D014409:Tumor Necrosis Factor-alpha; C461320:shosaiko-to; D016718:Arachidonic Acid; D017999:Leukotriene E4; C023384:fortimicin A; D011112:Polymyxin B; C035978:cefbuperazone; C047681:pranlukast