Actions of cytokines in relation to arachidonic acid metabolism and eicosanoid production

Peplow, P.V.

doi:10.1016/s0952-3278(96)90044-7

Cited by 33 publications

(14 citation statements)

References 103 publications

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“…10 Recent in vitro studies have also shown that the expression of some enzymes involved in eicosanoid metabolism is affected by various cytokines. 25 Both TNF-␣ and IL-1 increase the expression of phospholipase A2 and COX2 in various culture cells. 15 In contrast, the expression of COX1 is constitutive and less affected by cytokines.…”

Section: Discussionmentioning

confidence: 99%

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

Xiao

Patterson²,

Yang³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Because microvascular damage is a common feature of cerebral malaria, we have examined the role eicosanoid metabolites (prostaglandins and leukotrienes) in experimental cerebral malaria. Eighty ICR mice were infected with Plasmodium berghei ANKA, with 40 uninfected mice as controls. Half of the infected mice were treated on days 4 and 5 with aspirin, a prostaglandin synthesis inhibitor. Infected mice started to die of cerebral malaria on day 6, and by day 17, all infected mice died. In contrast, all infected mice treated with aspirin died by day 12. Infected mice had increased phospholipase A2 mRNA expression in the spleen and cyclooxygenase 1 (COX1) and COX2 expression in the brain. At the peak of cerebral malaria, infected mice had higher serum leukotriene B4 levels than control mice, and aspirin-treated infected mice had higher serum leukotriene B4 levels than untreated infected mice. These results suggest that prostaglandins are protective whereas leukotrienes are detrimental in cerebral malaria.Microvascular damage is a common feature of both primate and murine cerebral malaria. Humans who die of cerebral malaria caused by Plasmodium falciparum infection have petechial and ring hemorrhage and edema in the brain. [1][2][3][4][5][6] Similar findings are also seen in cerebral malaria of rhesus monkeys caused by P. coatneyi 7 and of mice caused by P. berghei ANKA. 8 The mechanisms involved in the induction of microvascular damage during cerebral malaria are not well studied. Because cerebral malaria is associated with the over-production of T helper-1 and proinflammatory cytokines (tumor necrosis factor-␣ [tnF-␣], interferon-␥ [IFN-␥], and interleukin-1 [IL-1]), 9-11 it is suggested that these cytokines cause cerebral malaria by up-regulation of intercellular adhesion molecule-1 (a cytoadhesion molecule involved in the adhesion of parasitized erythrocytes and mononuclear cells to endothelial cells) expression and nitric oxide production, which lead to mechanic blockage and disrupted neurotransmission. 11-13 However, whether endothelial blockage and activation themselves cause brain hemorrhage is not clear. The role of platelets in cerebral malaria has attracted some attention, although detailed pathways for the plateletinduced pathology have not yet been studied. 14 An alternative effect of the proinflammatory cytokines is the modulation on the production of eicosanoids (prostaglandins and leukotrienes), which are important in the maintenance of the structure and function of blood vessels. 15 Increased phospholipase A2 activities have been reported in adults infected with P. falciparum. 16 Children with cerebral malaria also have higher phospholipase A2 expression than those with uncomplicated malaria. 17 Because the expression of other enzymes such as cyclooxygenase 1 and 2 (COX1 and COX2) (for prostaglandin synthesis) and lipoxygenase (for leukotriene synthesis) in malaria infection is not known, it is not clear which eicosanoid pathway is involved in the pathogenesis. Malaria infection is known to ...

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Section: Discussionmentioning

confidence: 99%

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

Xiao

Patterson²,

Yang³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…[15][16][17] One of the responses to the production of proinflammatory cytokines is the synthesis of prostaglandins, which are important for the regulation of microvascular structure and permeability, fever, and immunosuppression. 12,18 Because brain hemorrhage, headache, fever, and immunosuppression are common in human malaria, we examined the production of PGE 2 . As expected, the production of PGE 2 increased in infected animals as the infection progressed.…”

Section: Discussionmentioning

confidence: 99%

Cytokine production in rhesus monkeys infected with Plasmodium coatneyi.

Yang¹,

Xiao²,

Tongren³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Plasmodium coatneyi infection in rhesus monkeys has been used as a model for studying human malaria. Cytokine production in this model, however, has so far not been examined. In this study, four rhesus monkeys were infected with P. coatneyi, with another four animals serving as uninfected controls. Blood samples were taken for the determination of daily parasitemia, and cytokine and prostaglandin E2 (PGE 2 ) levels at days 0, 3, 5, 7, and 10. All inoculated animals became infected, with synchronized appearance of ring-stage parasites. Infected monkeys had increased plasma levels of proinflammatory cytokines (interleukin-1␤, interferon-␥, and tumor necrosis factor-␣) during the late stage of the infection. They also had increased production of ciliary neurotrophic factor. In conjunction with the production of proinflammatory cytokines, infected monkeys also had gradual increases in the production of PGE 2 . A continued definition of the P. coatneyi/rhesus monkey animal model should be useful for the elucidation of the immunopathogenesis of human malaria.Laboratory animal models have been used in the studies of pathogenesis of human malaria, especially cerebral malaria, caused by Plasmodium falciparum infection. The laboratory animal model currently used by most researchers, P. berghei infection in mice, differs from human falciparum malaria in the nature of cells sequestered in the brain. In human P. falciparum infection, parasitized red blood cells (PRBC) bind to endothelial cells, whereas in the rodent model, leukocytes sequester in the brain. 1,2 In addition, T helper-1 (TH-1) and TH-2 cell responses in humans are much less polarized than those in mice. In humans, in addition to the typical TH-1 and TH-2 cytokines, TH-1 cells produce interleukin-10 (IL-10) (a Th-2 cytokine in the murine system), and TH-2 cells produce interferon-␥ (IFN-␥) (a TH-1 cytokine in the murine system). 3 Furthermore, human monocytes/macrophages produce several logs less nitric oxide than murine macrophages, and its regulation is under considerably different mechanisms. 4 Thus, the pathology of murine malaria is probably different from that of human malaria. 1,2 We and others have recently developed a nonhuman primate model for investigations of human malaria. 5 This model uses P. coatneyi infection in rhesus monkeys, and has pathologic characteristics similar to human cerebral malaria, such as the presence of knobs on PRBC, the binding of PRBC to endothelial cells, the expression of ligands on endothelial cells, and the pattern of sequestration in the brain. [5][6][7][8] Thus, this nonhuman primate malaria model has overcome some of the problems associated with the murine cerebral malaria model, and should be useful in studies in the pathogenesis of cerebral malaria.In this study, we have examined the plasma profile of cytokine production in rhesus monkeys infected with P. coatneyi. Because proinflammatory cytokines are considered important in the pathogenesis of malaria, 9-11 we have investigated changes of these cytokines ...

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“…2,5,7 The availability of specific COX-1 and COX-2 inhibitors, which have a high degree of specificity against pure enzyme preparations, should enable the determination of w hich enzyme produces which prostanoid in response to a specific stimulus.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Prostanoid production in the cyclooxygenase system is the result of the activity of at least tw o prostaglandin H synthase (cyclooxygenase, COX) enzymes, COX-1 and COX-2. 3 COX-1 is a constitutive enzyme, present in low levels, and believed to produce continuously present cytoprotective prostanoids.…”

Section: Introductionmentioning

confidence: 99%

The role of cyclooxygenase‐1 and cyclooxygenase‐2 in lipopolysaccharide and interleukin‐1 stimulated enterocyte prostanoid formation

Longo¹,

D'Amore²,

Mazuski³

et al. 1998

Mediators of Inflammation

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Lipopolysaccharide is an inflammatory agent and interleukin-1 is a cytokine. Their pro-inflammatory effects may be mediated by prostanoids produced by inducible cyclooxygenase-2. The aim of this study was to determine the prostanoids produced by lipopolysaccharide and interleukin-1 stimulated enterocytes through the cyclooxygenase-1 and 2 pathways. Cultured enterocytes were stimulated with lipopolysaccharide or interleukin-1beta with and without cyclooxygenase inhibitors. Low concentrations of indomethacin and valerylsalicylic acid (VSA) were evaluated as cyclooxygenase-1 inhibitors and their effects compared with the effects of a specific cyclooxygenase-2 inhibitor, SC-58125. Prostaglandin E2, 6-keto prostaglandin F1alpha, prostaglandin D2 and leukotriene B4 levels were determined by radioimmunoassay. Immunoblot analysis using isoform-specific antibodies showed that the inducible cyclooxygenase enzyme (COX-2) was expressed by 4 h in LPS and IL-1beta treated cells while the constitutive COX-1 remained unaltered in its expression. Interleukin-1beta and lipopolysaccharide stimulated the formation of all prostanoids compared with untreated cells, but failed to stimulate leukotriene B4. Indomethacin at 20 microM concentration, and VSA inhibited lipopolysaccharide and interleukin 1beta stimulated prostaglandin E2, but not 6-keto prostaglandin F1alpha formation. SC-58125 inhibited lipopolysaccharide and interleukin-1beta stimulated 6-keto prostaglandin F1alpha but not prostaglandin E2 release. The specific cyclooxygenase-2 inhibitor also inhibited lipopolysaccharide produced prostaglandin D2 but not interleukin-1beta stimulated prostaglandin D2. While SC-58125 inhibited basal 6-keto prostaglandin-F1alpha formation it significantly increased basal prostaglandin E2 and prostaglandin D2 formation. As SC-58125 inhibited lipopolysaccharide and interleukin-1beta induced 6-keto prostaglandin F1alpha production but not prostaglandin E2 production, it suggests that these agents stimulate prostacyclin production through a cyclooxygenase-2 mediated mechanism and prostaglandin E2 production occurs through a cyclooxygenase-1 mediated mechanism. Prostaglandin D2 production appeared to be variably produced by cyclooxygenase-1 or cyclooxygenase-2, depending on the stimulus.

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Actions of cytokines in relation to arachidonic acid metabolism and eicosanoid production

Cited by 33 publications

References 103 publications

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

Cytokine production in rhesus monkeys infected with Plasmodium coatneyi.

The role of cyclooxygenase‐1 and cyclooxygenase‐2 in lipopolysaccharide and interleukin‐1 stimulated enterocyte prostanoid formation

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