Phenomenon of Local Tissue Reactivity and Its Immunological, Pathological and Clinical Significance

Shwartzman, Gregory

doi:10.1097/00000441-193804000-00017

Cited by 36 publications

(26 citation statements)

References 21 publications

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“…Vascular effects of endotoxin Shwartzman (1937) and Andervont (1936) attributed the effect of endotoxin on established tumours to a haemorrhagic reaction. The changes produced by endotoxin in tumours are in many respects similar to a local Shwartzman reaction.…”

mentioning

confidence: 99%

Similarities of the Anti-tumour Actions of Endotoxin, Lipid A and Double-stranded RNA

Parr¹,

Wheeler²,

Alexander³

1973

Br J Cancer

119

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Summary.-Double stranded RNA (dsRNA) whether isolated from a fungal virus or prepared synthetically (i.e., Poly I Poly C) and endotoxin were found to exert very similar effects on syngeneic murine lymphomata and fibrosarcomata. They cause complete regressions of some established subcutaneous (s.c.) or intradermal (i.d.) tumours but not of intraperitoneal (i.p.) tumours when administered either systemically or directly into the tumour. To achieve this effect the tumours must be fully established and the best results were obtained when treatment was started 7 days after transplant. If treatment is started within the first 3 days following the transplantation of the tumour then only a slight inhibition of growth rate was observed. These agents can also act prophylactically and protect mice against a subsequent challenge but only if this is given i.p. and not if given s.c. or i.d. The prophylactic action is explained by the action of dsRNA and endotoxin on peritoneal macrophages which cause them to become cytotoxic to tumour cells (i.e., to become activated).The therapeutic effect of systemically administered endotoxin and dsRNA on established tumours is not the result of a direct action on the tumour cells themselves but is a complex process requiring the co-operation of several host factors. Haemorrhagic necrosis involving coagulation is essential (i.e., heparinization reduces the regression of tumours) but is not itself sufficient. Immunosuppression by whole body irradiation or by antilymphocyte serum also interferes with the antitumour action of dsRNA and endotoxin in spite of the fact that haemorrhagic necrosis still occurs. Also, the magnitude of the antitumour action correlated in a series of different tumours with their antigenicity. The observed tumour regressions are probably brought about by (1) vascular damage in the tumour which permits immune defence mechanisms of the host to gain access to the tumour and (2) activation of macrophages present within the tumour. The relative contribution of these two mechanisms may depend on the nature of the tumour and the route of administration of the active agents.Dibenyline, which protects against the lethal action of endotoxin by preventing the action of the catecholamines on the a-adrenergic receptors, makes it possible to increase the effectiveness of endotoxin in tumours by allowing a large dose to be given. Lipid A, a derivative of endotoxin which does not contain polysaccharide, has similar antitumour action to dsRNA and endotoxin. Some common features of the chemical structure of lipid A and dsRNA are discussed.Over a hundred years ago (Busch (Coley's toxin), which contained endotoxins 1866), a Viennese physician noted that amongst many other components, and regressions of some malignant tumours achieved some very striking results (cf. appeared to coincide with the occurrence review by Nauts, Fowler and Bogatko, of erysipelas. Coley, having made a 1953). The subject of the antitumour similar observation, deliberately treated action of endotoxins has attracte...

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mentioning

confidence: 99%

Similarities of the Anti-tumour Actions of Endotoxin, Lipid A and Double-stranded RNA

Parr¹,

Wheeler²,

Alexander³

1973

Br J Cancer

119

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“…Koch9s discovery that soluble bacterial material could trigger necrosis in a distant tuberculous site has some parallels with the SHWARTZMAN [153] reaction and subsequent experiments strengthen the parallel still further. For instance, injections of endotoxin-rich material into a distant site (instead of the tuberculin used by Koch) will also trigger necrosis in tuberculous lesions [154 -156], and injections into the flank of another cytokine trigger, muramyl dipeptide (MDP), caused necrosis in sites of inflammation due to complete Freund9s adjuvant [157].…”

Section: The Relationship Between the Koch Phenomenon And The Shwartzmentioning

confidence: 92%

M. tuberculosis: immunology and vaccination

2001

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Tuberculosis is increasing. Current treatment regimens require at least 6 months, because latent or stationary phase organisms are difficult to kill. Such regimens do not achieve full compliance, and "directly observed therapy short course" (DOTS) is having less impact than expected. This worrying situation is aggravated by coinfection with human immunodeficiency virus (HIV), and by the increase in drug-resistant strains.We need new insights that lead to more rapid therapies and immunotherapies, and more reliable vaccines.Recent insights have come from: understanding of the relationship between Mycobacterium tuberculosis and macrophages; the multiple T cell types that recognise mycobacterial peptides, lipids and glycolipids; the critical role of interferon-c (IFNc) and interleukin-12 (IL-12) in human mycobacterial infection revealed by genetically defective children; quantitation of the presence and importance of Th2 lymphocyte activation in human tuberculosis; the role of local conversion of inactive cortisone to active cortisol in the lesions; the recognition that some effective prophylactic vaccines also work as immumotherapeutics whereas others do not. In the longer term the recent sequencing of the M. tuberculosis genome will lead to further advances.In the short term, effective immunotherapy remains the most accessible breakthrough in the management of tuberculosis. The types of practical advance that will result from sequencing the genome are discussed speculatively, but cannot yet be predicted with certainty.

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“…suspension of bacteria at a concentration of 30 Biological tests on the lipopolysaccharides. These materials were tested for the ability to produce the following effects: (a) non-specific immunity by the method of Rowley (1956); ( b ) Schwartzman effect as described by Schwartzman (1937); ( c ) pyrogenic response. The rectal temperatures of rabbits were taken during 2 hr.…”

Section: Maintenance Of Culturesmentioning

confidence: 99%

Toxic Proteins from Vibrio cholerae and Water Vibrios which are Lethal for Mice

Jenkin

Rowley

1959

Journal of General Microbiology

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There is a marked tendency on the part of many research workers in the cholera field to assume that the manifestations of the disease are caused by a specific toxin which is liberated from the bacteria during growth. The proof of this hypothesis is difficult for two reasons. First, there is little precise information about the toxins of Vibrio cholma-e, and much confusion exists as to the chemical nature and similarity of those substances which have been described. The second difficulty is that it has not been possible to produce a disease resembling cholera in experimental animals; therefore it is difficult to test toxins for their ability to reproduce the signs of the natural disease. Burrows (1944) claimed to have extracted a highly toxic phospholipid from V. cholerae by using hot ethanol. This material contained, on occasion, 500 mouse LD 50 doseslmg. and, moreover, caused an increase in permeability to water of the small intestine of rabbits, when tested in. vitro. This effect on permeability was abolished by using intestines from animals immunized with V. choZerae. Freter (1956) described the isolation of two toxic fractions from V. chohae, one acid-soluble and the other insoluble in HC1 at pH 8.5. The acid-insoluble material had a mouse LD 50 of approximately 500-75Opg. and appeared to be a lipoprotein; the acid-soluble toxic material had a mouse toxicity of

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Phenomenon of Local Tissue Reactivity and Its Immunological, Pathological and Clinical Significance

Cited by 36 publications

References 21 publications

Similarities of the Anti-tumour Actions of Endotoxin, Lipid A and Double-stranded RNA

Similarities of the Anti-tumour Actions of Endotoxin, Lipid A and Double-stranded RNA

M. tuberculosis: immunology and vaccination

Toxic Proteins from Vibrio cholerae and Water Vibrios which are Lethal for Mice

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