Endotoxin (Salmonella abortus equi) in cancer patients. Clinical and immunological findings.
1. LPS phase I trial revealed MTD I of 1.0 ng/kg body weight and MTD II of 5.0 ng/kg body weight, the latter given together with ibuprofen (1,600 mg). 2. LPS phase II trial, using 4,0 ng/kg body weight plus ibuprofen in a biweekly schedule didn't show any response in patients with non-small cell lung cancer but 1 CR and 2 PR (13% response rate) in colorectal cancer patients. 3. The LPS tolerance is specific for each cytokine and mediator in regard to the kinetic and degree of its development. INF-gamma prevents the tolerance development to several cytokines with the exception of IL-8. 4. No tolerance was found in cell adhesion, phospholipase A2, and soluble TNF receptor I and II. Priming of ex vivo cytokine production of cytokines was found in mononuclear cells. 5. Synthetic LPS partial structure SDZ-MRL 953 (I) induces a cytokine pattern, which is profoundedly different from that of LPS, (II) with an inverse TNF to G-CSF relation, (III) is (without any ibuprofen treatment) remarkably low toxic, (IV) and downregulates the TNF-response to LPS markedly.
Department of Hematology/Oncology, University of Freiburg, Germany.
R
R
Engelhardt
F
F
Otto
A
A
Mackensen
R
R
Mertelsmann
C
C
Galanos
D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D004361:Drug Tolerance; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D012475:Salmonella
D016207:Cytokines; D008070:Lipopolysaccharides