Comparison of Leukocytic Pyrogen and Leukocytic Endogenous Mediator

Merriman, Charles R.; Pulliam, Larry A.; Kampschmidt, Ralph F.

doi:10.3181/00379727-154-39642

Cited by 75 publications

(28 citation statements)

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“…Even apyrogenic doses of endotoxin are able to produce hypoferremila in man, and the lowering of serum iron corresponds to accumulation of iron in reticuloendothelial cells (6). Similarly, intravenous injection of LP also results in acute hypoferremia (36). Moreover, LPinduced hypoferremia is dependent on neutrophils since it does not occur in neutropenic animals (2) and the factor in neutrophils responsible for lowering of serumii iron has been shown to be lactoferrin (3).…”

Section: Discussionmentioning

confidence: 99%

Human leukocytic pyrogen induces release of specific granule contents from human neutrophils.

Klempner¹,

Dinarello²,

Gallin³

1978

J. Clin. Invest.

197

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A B S T R A C T The ability of highly purified human leukocytic pyrogen (LP) to induce neutrophil lysosomal protein release is described. Human peripheral blood neutrophils isolated by Ficoll-Hypaquie and dextran sedimentation were exposed to purified human LP. The specific granule-associated proteins, lysozyme and lactoferrin were selectively released, whereas primary granule (,8-glucuronidase) and cytoplasmic (lactic dehydrogenase) enzyme markers were not. Optimum release was obsprved after 45 min in the presence of Ca++ and Mg++. Cytochalasin B (5 ,ug/ml) had no effect on LP-induced lysosomal enzyme release. Since the pyrogenicity of LP is dependent on prostaglandin synthesis, the effect of two potent inhibitors of prostaglandin synthesis on lysozyme release was studied. Both indomethacin and naproxen failed to inhibit specific granule protein release. These observations suggest that the concommitance of fever, elevated serum or urine lysozyme and hypoferremia may, in part, be explained by the interaction of LP and peripheral blood neutrophils.

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Section: Discussionmentioning

confidence: 99%

Human leukocytic pyrogen induces release of specific granule contents from human neutrophils.

Klempner¹,

Dinarello²,

Gallin³

1978

J. Clin. Invest.

197

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“…IL-1 has been functionally defined by its ability to stimulate a variety of target-cell specific responses in vivo (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). These include pyrogenicity, the ability to induce neutrophilia, and the stimulation of liver hepatocytes to produce acute-phase proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Appreviations used in this paper: ETAF, epidermal-derived thymocyte activating factor; IL-1, interleukin 1; LPS, lipopolysaccharide; pI, isoelectric point; PMA, phorbol myristate acetate; SAP, serum amyloid P (substance); SC, stratum corneum. row, lymphoid tissue, muscle, and liver (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Once believed to be produced only by activated macrophages, the synthesis and secretion of IL-1 or IL-1-like molecules has now been extended to a variety of cell types, including keratinocytes of the skin (15,16).…”

Section: Introductionmentioning

confidence: 99%

Presence of epidermal-derived thymocyte activating factor/interleukin 1 in normal human stratum corneum.

1985

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Keratinocytes produce a molecule, epidermal-derived thymocyte activating factor (ETAF), which is biologically and physiochemically similar to the polypeptide hormone interleukin 1 (IL-1). Because the stratum corneum (SC) is composed of terminally differentiated keratinocytes, we questioned whether ETAF/IL-1 could be isolated from this tissue. The extraction of normal human SC with a physiologic saline solution yielded a large amount of ETAF/IL-1 activity, as measured by the in vitro thymocyte co-stimulator assay. SC-derived ETAF/IL-1 (scETAF/IL-1) eluted from a sizing column with an approximate molecular weight of 15,000, and demonstrated three isoelectric point forms after separation on a chromatofocusing column. By these physiochemical characteristics, scETAF/IL-1 was found to be similar, if not identical to human keratinocyte-and macrophage-derived ETAF/IL-1. Further, a number of biologic effects known to occur in vivo after the administration of ETAF/ IL-1, such as fever, neutrophilia, and an increase in plasma levels of acute-phase proteins, were all induced by the injection of scETAF/IL-1 into endotoxin-nonresponsive mice. scETAF/IL-1 was also found to stimulate collagenase production by human fibroblasts in vitro. In summary, our studies have established that normal human SC contains a large quantity of scETAF/IL-1. Whether scETAF/IL-1 integrates into the earliest afferents phases of local inflammatory responses, or merely represents a means of disposal of excessively produced hormone is currently unresolved.

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“…11 Increasing knowledge of host -parasite interactions has provided insights into the pathogenesis of malaria and hence the identification of new candidate genes. Interleukin-1 (IL1) is a potent endogenous pyrogen and inducer of the acute phase response, 12 and these innate immune responses are an important part of the human host's initial reaction to infection by the malaria parasite. TNFA is also an endogenous pyrogen and variants of this gene have been associated with cerebral malaria, 6,13,14 suggesting that functionally similar molecules, such as IL1, are good candidate genes for susceptibility to malaria.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria in a Gambian case–control study

et al. 2003

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Interleukin-1 (IL1) is a potent endogenous pyrogen and inducer of the acute phase response, and these innate immune responses are an important part of the human host's initial reaction to infection by the malaria parasite. In addition, several single-nucleotide polymorphisms (SNPs) in this region have previously been demonstrated to be associated with susceptibility to infectious disease. Therefore, a possible association with malaria susceptibility was investigated. A total of 13 polymorphic markers were used in a two-stage screening strategy to genotype a Gambian case -control study group by either restriction endonuclease digestion or the Sequenom MassARRAYt assay. This involved an initial screen of 188 severe cases and 188 mild controls, and if there was a significant association with a malaria phenotype (Po0.05); this was followed by screening of the remaining 1044 samples. Two markers showed significant association with malaria: interleukin-1 alpha þ 4845 G-T (P ¼ 0.035 for mild malaria versus controls) and interleukin-1 beta þ 3953 C-T (P ¼ 0.030 for mild malaria versus severe malaria). Haplotypes constructed using the SNPHAP programme were not associated with any of the malaria phenotypes investigated. In summary, if IL1 variants are involved in malaria susceptibility in the Gambia at all, then the effects are small.

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Comparison of Leukocytic Pyrogen and Leukocytic Endogenous Mediator

Cited by 75 publications

References 0 publications

Human leukocytic pyrogen induces release of specific granule contents from human neutrophils.

Human leukocytic pyrogen induces release of specific granule contents from human neutrophils.

Presence of epidermal-derived thymocyte activating factor/interleukin 1 in normal human stratum corneum.

Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria in a Gambian case–control study

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