Evidence for the involvement of interleukin 6 in experimental cancer cachexia.
Journal of Clinical InvestigationPublished 1 May 1992Open access
Gideon Strassmann, M Fong, J S Kenney, Chaim O. Jacob
Citations656
SJR quartileQ1
SJR score4.72
SNIP2.17
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Evidence is presented to support a role for interleukin (IL-6) as a cachectic factor in the development of cancer cachexia in this model system, and monoclonal antibody to murine IL-6 (but not anti-tumor necrosis factor antibody) was able to significantly suppress theDevelopment of key parameters of Cachexia in tumor bearing mice.
Abstract
In this report we describe an experimental model of cachexia that fulfills the criteria of an early effect with a small tumor mass not related to the growth rate of the tumor, and progressive wasting of muscle and fat without a detectable loss of appetite. C-26.IVX is a cell line derived from murine colon-26 adenocarcinoma which retains the transplantability of the original tumor and induces true cachexia in syngeneic hosts. Evidence is presented to support a role for interleukin (IL-6) as a cachectic factor in the development of cancer cachexia in this model system. Thus, increasing levels of IL-6 in C-26.IVX-bearing mice correlate with the development of cachexia. If the primary tumors were resected, mice gained weight and the levels of IL-6 in the serum were reduced significantly. Moreover, monoclonal antibody to murine IL-6 (but not anti-tumor necrosis factor antibody) was able to significantly suppress the development of key parameters of cachexia in tumor bearing mice.
Keywords
MedicineNursing
Analytical BiochemistryQuantitative estimation of proteins by electrophoresis in agarose gel containing antibodies
4,431 Citations1966Carl‐Bertil Laurell
The method utilizes the difference between the rate of electrophoretic migration of proteins and of their antibody complexes in agarose gel to perform quantitative analysis of proteins with a charge differing from that of the bulk of the immunoglobulins.
The Journal of Experimental MedicinePurification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells.
826 Citations1985Bruce Beutler, James A. Mahoney +3 more
The purification of cachectin to apparent homogeneity and characterization of its receptor should facilitate further investigations into the role of Cachectin and other macrophage mediators in the metabolic derangements that occur during infection and cachexia.
The Journal of Experimental MedicineCachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.
740 Citations1988Kevin J. Tracey, Wei He +8 more
Data suggests that the exposure of the normal host to cachectin is capable of inducing a pathophysiological syndrome of cachexia, anemia, and inflammation similar to that observed during inflammatory states or malignancy.
The Journal of Experimental MedicineAn antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis.
694 Citations1990Nancy H. Ruddle, Cheryl M. Bergman +5 more
It is suggested that LT and TNF-alpha and the T cells that produce them play an important role in EAE, and treatment of recipient mice with an antibody that neutralizesLT and T NF-alpha prevents transfer of clone-mediated EAE.
CellTumors secreting human TNF/cachectin induce cachexia in mice
640 Citations1987Allen Oliff, Deborah Defeo-Jones +6 more
It is concluded that mice bearing tumors that secrete TNF/cachectin develop progressive wasting and die more quickly than mice bearing control tumors.
PubMedTumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure.
600 Citations1975Thomas H. Corbett, Daniel P. Griswold +3 more
Four colon tumors survived the first transplant and are now in serial passage, and two tumors are highly metastatic, and at least one of these is known to be suitable for surgery-chemotherapy adjuvant studies.
The LancetEVIDENCE FOR TUMOUR NECROSIS FACTOR/CACHECTIN PRODUCTION IN CANCER
425 Citations1987Frances R. Balkwill, Frances Burke +6 more
Labile tumour-necrosis-factor-like (TNF) activity was detected by means of an enzyme-linked immunosorbent assay in 50% of 226 freshly obtained serum samples from cancer patients with active disease, but the inducing stimulus and the clinical significance of TNF production in cancer are not understood.
The Journal of ImmunologyGeneration and characterization of hamster monoclonal antibodies that neutralize murine tumor necrosis factors.
380 Citations1989Kathleen C. F. Sheehan, Nancy H. Ruddle +1 more
TN3-19.12 injected into mice subsequently treated with LPS prevented the detection of TNF in the circulation by either assay and protected mice from the lethal effects of endotoxin shock.
The Journal of ImmunologyAnti-IL-6 monoclonal antibodies protect against lethal <i>Escherichia coli</i> infection and lethal tumor necrosis factor-<i>alpha</i> challenge in mice.
325 Citations1990H. Fletcher Starnes, M K Pearce +4 more
IL-6 is a mediator in lethal E. coli infection, and antagonists of IL-6 may be beneficial therapeutically in life-threatening bacterial infection, according to a mouse model of septic shock.
The FASEB JournalAnticachectin/tumor necrosis factor‐α antibodies attenuate development of cachexia in tumor models
209 Citations1989Barbara Sherry, J Gélin +7 more
It is concluded that an endogenous cachectin response, inhibitable by exogenously administered antibody, contributes to anorexia and to changes in body fat and protein metabolism in these tumor‐bearing animals.
EndocrinologyChinese Hamster Ovarian Cells Transfected with the Murine lnterleukin-6 Gene cause Hypercalcemia as well as Cachexia, Leukocytosis and Thrombocytosis in Tumor-Bearing Nude Mice
203 Citations1991Karen Black, I. Ross Garrett +1 more
PubMedExperimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice.
200 Citations1990Yutaka Tanaka, Hiroyuki Eda +7 more
Mice bearing colon 26 is an appropriate model for elucidating the mechanism that causes cachexia and noncachectic mice with Meth A fibrosarcoma gained weight, which was somewhat less than the control, and had neither hypoglycemia nor hypercorticism, although some mild disorders of hepatic functions were found.
Hematology/Oncology Clinics of North AmericaMechanisms of Cancer Cachexia
169 Citations1991Howard N. Langstein, Jeffrey A. Norton
Further study into the mechanisms and possible treatment of cancer cachexia is needed, because a large proportion of cancer patients who are incurable by current therapies continue to suffer from this lethal wasting diathesis and specific strategies to reverse the cachectic changes associated with cancer will likely improve antitumor treatment.
Scandinavian Journal of ImmunologyDetection of Tumour Necrosis Factor‐Like Cytotoxicity in Serum from Patients With Septicaemia but Not from Untreated Cancer Patients
130 Citations1986Anders Waage, Terje Espevik +1 more
In 23 untreated patients with malignant disease of varying origin and stage, including two patients with severe cachexia, the authors were not able to detect tumour necrosis factor‐like cytotoxic activity in serum from three patients in the initial phase of septicaemia.
JNCI Journal of the National Cancer InstituteTumor Necrosis Factor Not Detectable in Patients With Clinical Cancer Cachexia
129 Citations1988Susan H. Socher, D. Martínez +3 more
To assess the relationship between TNF and weight loss among cancer patients, serum levels in serum were assayed from 19 patients who had lost 8%-40% of premorbid weight and no TNF was detected.
Clinical PhysiologyInterleukin 1, tumour necrosis factor‐alpha (cachectin) and the pathogenesis of cancer cachexia
129 Citations1987Lyle L. Moldawer, Michael Georgieff +1 more
If monokines serve as metabolic inducers, then efforts to block therapeutically the actions of macrophage-secreted substances may play a role in slowing the progression of tissue-wasting associated with catabolic states, particularly due to malignant tumours.
The Journal of ImmunologyIn vivo induction of IL-6 by administration of exogenous cytokines and detection of de novo serum levels of IL-6 in tumor-bearing mice.
117 Citations1989Joe McIntosh, David M. Jablons +5 more
Although the exact role of IL-6 in TB animals remains to be elucidated, its known pleotrophic immune and metabolic effects may be important in the host response to malignancy.
CellThe role of tumor necrosis factor (cachectin) in cachexia
115 Citations1988A Oliff
Recent results from animal models and early clinical trials of tumor necrosis factor/cachectin are discussed, which suggest a resolution of this problem of conflict between two critical biologic responses to tumor cell lysis and nutritional homeostasis.
PubMedThe roles of gamma-interferon and tumor necrosis factor alpha in an experimental rat model of cancer cachexia.
109 Citations1991H N Langstein, Gerard M. Doherty +3 more
It is suggested that gamma-interferon may be an important mediator of cachexia in this rat tumor model and that passive immunization against it can partially reverse the cachectic changes associated with cancer and prolong survival.
Annals of SurgeryChronic TNF Infusion Causes Anorexia But Not Accelerated Nitrogen Loss
88 Citations1989H. R. Michie, Matthew L. Sherman +4 more
TNF may represent the primary afferent stimulus inducing many of the metabolic changes that occur during critical illness, but it is not solely responsible for the accelerated net proteolysis that occurs in these patients.
Critical Reviews in Oncology/HematologyCancer cachexia
61 Citations1987Jeffrey A. Norton, James Peacock +2 more
Nutritional support can reverse some of the derangements seen with cachexia, and there is evidence that functional lean body mass or body cell mass can be restored in some (but not all) patients, but nutritional support has not yet improved response to chemotherapy or radiation therapy, nor has it improved host tolerance of chemotherapy.
PubMedInterleukin 4 inhibits stimulation of hepatic lipogenesis by tumor necrosis factor, interleukin 1, and interleukin 6 but not by interferon-alpha.
48 Citations1991Carl Grünfeld, Mounzer Soued +5 more
It is demonstrated that interleukin 4 can inhibit the metabolic action of selected cytokines, which provides strong support for the proposal that lipogenic cytokines operate through 2 distinct mechanisms of action and can therefore be divided into 2 separate classes based on their interactions.
The Journal of ImmunologyRegulation of murine mononuclear phagocyte inflammatory products by macrophage colony-stimulating factor. Lack of IL-1 and prostaglandin E2 production and generation of a specific IL-1 inhibitor
23 Citations1991Gideon Strassmann, Donald R. Bertolini +2 more
Conditioned medium from macrophage cultures treated with purified L929 or human rM-CSF in combination with LPS exhibited a significant reduction of IL-1 bioactivity as compared with an LPS challenge alone, and this data suggest that M- CSF may play a role in the down-regulation of inflammatory responses.