Immunology of Pyelonephritis in the Primate Model

Roberts, James A.; Roth, J; Domingue, Gerald J.; Lewis, Ronald W.; Kaack, Bernice; Baskin, Gary B.

doi:10.1016/s0022-5347(17)53516-8

Cited by 98 publications

(34 citation statements)

References 15 publications

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“…In fact, both macrophages and neutrophils may have liberated a variety of cytokines (tumor necrosis factor and interleukins), metabolites of arachidonic acid, and noxious inflammatory mediators such as oxygen radicals and lysosomal enzymes during the process of phagocytosis, which may have accounted for the deleterious effects to kidney cells. While inhibition of acute suppuration by cyclophosphamide-induced neutropenia (9) or antioxidant therapy with radical scavengers such as superoxide dismutase (37) and even complement depletion with cobra venom factor (38) have all been reported to reduce kidney damage after infection, the present study reports a major protective role for a leukotriene inhibitor in pyelonephritis.…”

Section: Discussionmentioning

confidence: 53%

“…For example (17,37), the presence of bacteria in the renal parenchyma during pyelonephritis induces a marked local cellular and humoral response. Inflammatory cells such as polymorphonuclear cells (PMNs) migrate into the interstitium under chemotactic stimuli and then release free oxygen radicals (02 -, OH, and H202) and lysosomal enzymes into their environment.…”

mentioning

confidence: 99%

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L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis

Tardif

Beauchamp

Bergeron

et al. 1994

Antimicrob Agents Chemother

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In this study, the relationship between leukotrienes, peritubular cell infiltration with polymorphonuclear cells (PMNs) and renal tubular damage was investigated in a rat model of acute ascending pyelonephritis.Infection was induced by the injection of 105 CFU of Escherichia coli into the bladder and occlusion of the left ureter for 24 h. Treatment of infected animals was started 24 h after the induction of pyelonephritis with either hydrocortisone (25 mg/kg of body weight per day), the leukotriene inhibitor L-651,392 (10 mg/kg/day), or the vehicle of L-651,392 and was maintained for 5 days. At the end of treatment, the animals were killed, serum was collected, and both kidneys were removed for colony counts and histopathology. Renal function was evaluated by the measurement of blood urea nitrogen levels and creatinine clearance. The numbers of PMNs and mononuclear cells (MNs) in the cortex and medulla were recorded for all groups on plastic sections done from the left kidney. Infection alone (vehicle of L-651,392) resulted in intensive interstitial infiltration and a severe tubular destruction in the cortex. Treatment with hydrocortisone did not prevent PMN migration and tissue damage. By contrast, treatment with L-651,392 resulted in a significant reduction in PMNs (P < 0.001 in comparisons with all other groups) and greater preservation of the tubular structure despite identical bacterial counts than in the group receiving hydrocortisone. We conclude that L-651,392 prevents inflammatory cells from reaching the site of infection and protects the kidney from tubular damage associated with inflammation during pyelonephritis. Inhibitors of leukotrienes should be further investigated for their potential benefit as adjuvants to antibiotherapy in the treatment of pyelonephritis.Several studies support the hypothesis that acute inflammation plays a major role in the development of tissue damage during infection. For example (17,37), the presence of bacteria in the renal parenchyma during pyelonephritis induces a marked local cellular and humoral response. Inflammatory cells such as polymorphonuclear cells (PMNs) migrate into the interstitium under chemotactic stimuli and then release free oxygen radicals (02 -, OH, and H202) and lysosomal enzymes into their environment. Although these products are essential for bacterial killing, they are in part responsible for deleterious effects to host cells, including tissue damage and scar formation, with the ensuing decreased renal function as well as permanent kidney damage.While the C5a fraction of complement may initiate the migration of PMNs in the early phase of the infection (38), the potent chemotactic leukotriene B4 (LTB4) and also the cysteinyl leukotrienes LTC4, -D4, and -E4 are suspected of playing an important role in the outcome of pyelonephritis. Infiltrating leukocytes and cells from the rat glomeruli can produce leukotrienes (2, 11). Their synthesis is stimulated by bacterial components such as endotoxin. Studies of septic shock and different diseases of the lu...

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Section: Discussionmentioning

confidence: 53%

mentioning

confidence: 99%

L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis

Tardif

Beauchamp

Bergeron

et al. 1994

Antimicrob Agents Chemother

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“…However, from our data it is impossible to ascertain whether the SOD activities per cell are really changing during the cell cycle, because we are determing the activités in SOD relative to total pro tein and not the SOD content per cell as a process of time. Similar criticism as to the analysis of SOD activity has already been reported [6], The half-life of SOD in the blood is less than 6 min, but SOD is excreted by the kid neys [15]. Subsequently any effect of SOD is probably influenced by urinary or renal SOD activity.…”

Section: Totalmentioning

confidence: 60%

Superoxide Dismutase Activity in Renal Cell Carcinoma

Nakada

Akiya²,

Koike³

et al. 1988

Eur Urol

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“…Roberts et al [4] also reported that SOD reduced the damage to renal tubular cells in an acute pyelonephritis model, suggesting that superoxide leads to a loss of renal tissue and function, and so-called chronic pyelonephritis.…”

Section: Suppression O F Enhanced Renal Scarring By Peg-sodmentioning

confidence: 97%

“…Phorbol myristate ace tate (PMA) has been reported to stimulate the PMNs into releasing superoxide via an activation of protein kinase C [4], In this study, we examined the effects of PMA on renal scarring following infection. …”

Section: Introductionmentioning

confidence: 99%

Renal Scarring Is Enhanced by Phorbol Myristate Acetate following Infection with Bacteria with Mannose-Sensitive Pili

Matsumoto¹,

Haraoka²,

Mizunoe³

et al. 1993

Nephron

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Renal scarring is considered to develop in the later stages of chronic pyelonephritis. In our experimental model of pyelonephritis, bacteria with mannose-sensitive (MS) pili on their surface promoted renal scarring following inoculation into the renal parenchyma. The administration of cyclophosphamide to induce leukopenia and of superoxide dismutase to inactivate superoxide released from polymorphonuclear leukocytes (PMN) at the infection site suppressed any renal scarring following the infection. Conversely, the administration of phorbol myristate acetate at an early stage of infection significantly enhanced the renal scarring. These findings suggest that the PMNs which infiltrate the infection site and the superoxide they release play an important role in any renal scarring following infection with MS-piliated bacteria.

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Immunology of Pyelonephritis in the Primate Model

Cited by 98 publications

References 15 publications

L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis

L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis

Superoxide Dismutase Activity in Renal Cell Carcinoma

Renal Scarring Is Enhanced by Phorbol Myristate Acetate following Infection with Bacteria with Mannose-Sensitive Pili

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