The control of rheumatic disease by endogenous protein

Lewis, David; Capstick, R B; Best, R.

doi:10.1016/0006-2952(76)90118-0

Cited by 13 publications

(4 citation statements)

References 9 publications

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“…Increased spermine levels have been measured in tissues following injury, inflammation, and infection, derived in part from the release of intracellular spermine from dying and injured cells, and in part by stimulated biosynthesis (23). It has been suggested that the accumulation of spermine, and the products of its oxidative metabolism via polyamine oxidase, mediate the anti-inflammatory activity found in inflammatory exudates, human pregnancy serum, plasma from arthritic rats, and human rheumatoid synovial fluid (21,(24)(25)(26)(27)(28). Although these and other studies implicate spermine in suppressing the innate immune response, it was unclear whether it might also counterregulate proinflammatory cytokine synthesis.…”

mentioning

confidence: 99%

Spermine Inhibits Proinflammatory Cytokine Synthesis in Human Mononuclear Cells: A Counterregulatory Mechanism that Restrains the Immune Response

Zhang¹,

Caragine

Wang

et al. 1997

The Journal of Experimental Medicine

285

239

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The local production of proinflammatory cytokines mediates the host response to inflammation, infection, and injury, whereas an overexpression of these mediators can injure or kill the host. Recently, we identified a class of multivalent guanylhydrazone compounds that are effective inhibitors of proinflammatory cytokine synthesis in monocytes/macrophages. The structure of one such cationic molecule suggested a molecular mimicry with spermine, a ubiquitous endogenous biogenic amine that increases significantly at sites of inflammation and infection. Here, we addressed the hypothesis that spermine might counterregulate the innate immune response by downregulating the synthesis of potentially injurious cytokines. When spermine was added to cultures of human peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS), it effectively inhibited the synthesis of the proinflammatory cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, MIP-1α, and MIP-1β. The inhibition of cytokine synthesis was specific and reversible, with significant inhibition of TNF synthesis occurring even when spermine was added after LPS. The mechanism of spermine-mediated cytokine suppression was posttranscriptional and independent of polyamine oxidase activity. Local administration of spermine in vivo protected mice against the development of acute footpad inflammation induced by carrageenan. These results identify a distinct molecular counterregulatory role for spermine in downregulating the monocyte proinflammatory cytokine response.

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mentioning

confidence: 99%

Spermine Inhibits Proinflammatory Cytokine Synthesis in Human Mononuclear Cells: A Counterregulatory Mechanism that Restrains the Immune Response

Zhang¹,

Caragine

Wang

et al. 1997

The Journal of Experimental Medicine

285

239

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“…Anti-inflammatory activities have beer claimed for some high MW proteins [11][12][13] Some, but apparently not all of these endo genous anti-inflammatory substances may ow, their anti-inflammatory properties to a counte irritant action [13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Inflammation, counter irritation and rat serum acute phase α2-macroglobulin levels

Baldo¹

1982

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Following the injection of turpentine and carrageenan into rats, laboratory models for counter irritation were assessed by measuring changes in paw thicknesses and serum acute phase alpha 2-macroglobulin concentrations. Both indices of inflammation were also examined in groups of rats dosed with 6-mercaptopurine, the best inhibitor found so far of elevated levels of alpha 2-macroglobulin in rat serum. Results showed that there is no relationship between the degree of irritant-induced inhibition of inflammation and the serum concentration of the acute phase protein. Hence, at least in the models for counter irritation used in this study, alpha 2-macroglobulin cannot be viewed as an endogenous anti-inflammatory protein.

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“…Since then such activity has been reported in granuloma pouch exudate in intact and adrenalectomized rats [2] arthritic and normal rat plasma [3,4] human pregnancy serum [5] anti-lymphocytic serum [6] human peritoneal fluid [7] extracts from regenerating rat liver damaged in vivo by dimethylnitrosamine (DMNO) [8] sponge-induced exudates in rat [9] and in human rheumatoid synovial fluid [10].…”

Section: Introductionmentioning

confidence: 99%

Putrescine — a potent endogenous anti-inflammatory substance in inflammatory exudates

1983

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Sponge-induced exudate from the rat and saline extracts of normal rat liver and rat liver damaged in situ by dimethylnitrosamine have been assayed for putrescine, spermidine and spermine levels. The three physiological oligoamines have been examined for anti-inflammatory activity by the carrageenan-induced oedema rat model and spermidine and putrescine were found to be anti-inflammatory with putrescine being about ten times as active as spermidine. Putrescine was also anti-inflammatory in the adjuvant arthritic rat model. Thioacetamide and theophylline were also anti-inflammatory and theophylline doubled the level of putrescine in rat liver. It was concluded that putrescine was a potent anti-inflammatory factor in the inflammatory exudates and extracts examined.

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The control of rheumatic disease by endogenous protein

Cited by 13 publications

References 9 publications

Spermine Inhibits Proinflammatory Cytokine Synthesis in Human Mononuclear Cells: A Counterregulatory Mechanism that Restrains the Immune Response

Spermine Inhibits Proinflammatory Cytokine Synthesis in Human Mononuclear Cells: A Counterregulatory Mechanism that Restrains the Immune Response

Inflammation, counter irritation and rat serum acute phase α2-macroglobulin levels

Putrescine — a potent endogenous anti-inflammatory substance in inflammatory exudates

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