Evidence that tumor necrosis induced by aminated beta 1-3D polyglucose is mediated by a concerted action of local and systemic cytokines.
Aminated beta 1-3D polyglucose (AG) causes regression of Meth A sarcoma in syngeneic mice when injected systemically on day 7 after tumour inoculation. AG does not concentrate in the tumour, but distributes throughout the body. AG treatment causes release of large amounts of interleukin 1 (IL-1) both in vivo and in macrophage cultures in vitro. AG is a weak stimulus for tumour necrosis factor (TNF) release both in vitro and in vivo. However, tumour tissue and sera from untreated mice on days 3 and 7 after inoculation contain significant amounts of TNF, whereas tumour tissue and sera on day 14 contain insignificant amounts of TNF. This correlates exactly with the sensitivity to AG treatment. IL-1, and TNF when injected locally cause reduction in tumour blood circulation and also shrinkage of the tumour. All these facts taken together indicate that the tumour circulatory failure and necrosis induced by AG are mediated by local TNF-unrelated to the treatment--potentiated by systemic cytokines triggered by the AG.
Seljelid
R
R
Institute of Medical Biology, University of Tromsø, Norway.
Figenschau
Y
Y
Bøgwald
J
J
Rasmussen
L T
LT
Austgulen
R
R
D000818:Animals; D046508:Culture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D005936:Glucans / Q000493:pharmacokinetics / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000032:analysis / Q000188:drug therapy* / Q000276:immunology; D012878:Skin Neoplasms / Q000032:analysis / Q000188:drug therapy / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D047071:beta-Glucans
D005936:Glucans; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; C033363:beta-1,3-glucan