Chloroquine inhibits proinflammatory cytokine release into human whole blood

1998 ◽  
Vol 274 (4) ◽  
pp. R1058-R1064 ◽  
Author(s):  
Ina Karres ◽  
Jean-Pierre Kremer ◽  
Ingrid Dietl ◽  
Ursula Steckholzer ◽  
Marianne Jochum ◽  
...  

Excessive synthesis and release of proinflammatory cytokines during endotoxemia causes severe pathophysiological derangements and organ failure. Because the lysosomotropic agent chloroquine has been effective in the treatment of diseases associated with increased secretion of proinflammatory cytokines such as malaria or rheumatoid arthritis, this study evaluates the potential effect of chloroquine on endotoxin-induced cytokinemia using human whole blood from healthy volunteers. Chloroquine revealed a dose-dependent inhibitory effect on endotoxin-induced secretion of tumor necrosis factor-α, interleukin-1β, and interleukin-6 that was associated with reduced cytokine mRNA expression. Moreover, ammonia and methylamine, which react as weak bases like chloroquine, reduced synthesis and secretion of proinflammatory cytokines. These data indicate a potent anti-inflammatory effect of chloroquine on endotoxin-induced synthesis of proinflammatory cytokines that may be due to its weak base effect. Thus chloroquine may be of therapeutic benefit not only during chronic inflammation but also in diseases that are related to bacteria-induced inflammation.

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 278
Author(s):  
Yun Mi Lee ◽  
Eunjung Son ◽  
Dong-Seon Kim

Sam-Myo-Whan (SMW) has been used in Korean and Chinese traditional medicine to help treat gout, by reducing swelling and inflammation and relieving pain. This study compared the effects of SMW extracted by using different solvents, water (SMWW) and 30% EtOH (SMWE), in the treatment of gouty arthritis. To this end, we analyzed the main components of SMWW and SMWE, using high-performance liquid chromatography (HPLC). Anti-hyperuricemic activity was evaluated by measuring serum uric acid levels in hyperuricemic rats. The effects of SMWW and SMWE on swelling, pain, and inflammation in gouty arthritis were investigated by measuring affected limb swelling and weight-bearing, as well as by enzyme-linked immunosorbent assays, to assess the levels of proinflammatory cytokines and myeloperoxidase (MPO). In potassium oxonate (PO)-induced hyperuricemic rats, SMWW and SMWE both significantly decreased serum uric acid to similar levels. In monosodium urate (MSU)-induced gouty arthritis mice, SMWE more efficiently decreased paw swelling and attenuated joint pain compare to SMWW. Moreover, SMWE and SMWW suppressed the level of inflammation by downregulating proinflammatory cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6) and MPO activity. HPLC analysis further revealed that berberine represented one of the major active ingredients demonstrating the greatest change in concentration between SMWW and SMWE. Our data demonstrate that SMWE retains a more effective therapeutic concentration compared to SMWW, in a mouse model of gouty arthritis.


2005 ◽  
Vol 10 (1) ◽  
pp. 39-44 ◽  
Author(s):  
G. Patrick Lambert ◽  
John R. Spurzem ◽  
Debra J. Romberger ◽  
Todd A. Wyatt ◽  
Elizabeth Lyden ◽  
...  

ACS Sensors ◽  
2016 ◽  
Vol 1 (12) ◽  
pp. 1432-1438 ◽  
Author(s):  
Cheng Jiang ◽  
Muhammad Tanzirul Alam ◽  
Saimon Moraes Silva ◽  
Safura Taufik ◽  
Sanjun Fan ◽  
...  

1988 ◽  
Vol 59 (03) ◽  
pp. 378-382 ◽  
Author(s):  
Gyorgy Csako ◽  
Eva A Suba ◽  
Ronald J Elin

SummaryThe effect of purified bacterial endotoxin was studied on human platelets in vitro. In adding up to 1 μg/mL of a highly purified endotoxin, we found neither aggregation nor ATP release in heparinized or citrated human platelet-rich plasma. On the other hand, endotoxin at concentrations as low as a few ng/mL (as may be found in septic patients) caused platelet aggregation in both heparinized and citrated human whole blood, as monitored by change in impedance, free platelet count, and size. Unlike collagen, the platelet aggregation with endotoxin occurred after a long lag phase, developed slowly, and was rarely coupled with measurable release of ATP. The platelet aggregating effect of endotoxin was dose-dependent and modified by exposure of the endotoxin to ionizing radiation. Thus, the activation of human platelets by “solubilized” endotoxin in plasma requires the presence of other blood cells. We propose that the platelet effect is mediated by monocytes and/or neutrophils stimulated by endotoxin.


Blood ◽  
2020 ◽  
Vol 136 (2) ◽  
pp. 183-198 ◽  
Author(s):  
Hanqing He ◽  
Panglian Xu ◽  
Xiaofei Zhang ◽  
Min Liao ◽  
Qiongye Dong ◽  
...  

Abstract Hematopoietic stem cell (HSC) aging correlates with an increasing risk of myeloproliferative disease and immunosenescence. In this study, we show that aging-related inflammation promotes HSC aging through tumor necrosis factor-α (TNF-α)→ERK→ETS1→interleukin27Ra (IL27Ra) pathway. TNF-α, a well-known biomarker of inflammation, increases during aging and induces the expression of IL27Ra on HSCs via ERK-ETS1 signaling. Deletion of IL27Ra rescues the functional decline and myeloid bias of HSCs and also reverses the inhibitory effect of TNF-α on HSCs. Aged IL27Ra−/− mice had a reduced proportion of myeloid-biased HSCs and did not display the biased myeloid differentiation that occurs in aged wild-type mice. IL27Ra+ HSCs exhibit impaired reconstitution capacity and myeloid-bias compared with IL27Ra− HSCs and serve as a myeloid-recovery pool upon inflammatory insult. Inflammation-related genes were enriched in IL27Ra+ HSCs and this enrichment increases with aging. Our study demonstrates that age-induced IL27Ra signaling impairs HSCs and raises the possibility that interfering with IL27Ra signaling can counter the physiologically deleterious effect of aging on hematopoietic capacity.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Ivan M. Petyaev ◽  
Nayilia A. Zigangirova ◽  
Elena Y. Morgunova ◽  
Nigel H. Kyle ◽  
Elena D. Fedina ◽  
...  

Resveratrol (RESV), an antifungal compound from grapes and other plants, has a distinct ability to inhibit theChlamydia (C.) trachomatisdevelopmental cycle in McCoy cells, a classic cell line used for chlamydial research. Inoculation ofC. trachomatiswith increasing amounts of RESV (from 12.5 to 100 μM) gave a dose-dependent reduction in the number of infected McCoy cells visualized by using monoclonal antibodies against chlamydial lipopolysaccharide. A similar trend has been observed with immunoassay for major outer membrane protein (MOMP). Furthermore, there was a step-wise reduction in the number ofC. trachomatisinfective progenies caused by the increasing concentrations of RESV. The ability of RESV to arrestC. trachomatisgrowth in McCoy cells was confirmed by a nucleic acid amplification protocol which revealed dose-dependent changes in mRNAs for different genes of chlamydial developmental cycle (euo,incA, andomcB). Although the precise nature of the antichlamydial activity of RESV is yet to be determined and evaluated in future studies, the observed effect of RESV onC. trachomatisinfection was not related to its potential effect on attachment/entry of the pathogen into eukaryotic cells or RESV toxicity to McCoy cells. Similar inhibitory effect was shown forC. pneumoniaeandC. muridarum.


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