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The thermal potentiation of acetaminophen-inhibited PMN oxidative metabolism in vitro
1Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Abstract:
The effect of high temperatures (39, 41, and 43 degrees C) on acetaminophen (AM-) induced inhibition of the oxidative respiratory burst of polymorphonuclear leukocytes (PMNs) in vitro has been examined. Whole blood or isolated human PMNs were exposed to various temperatures in vitro in the presence or absence of AM for 0-90 min. Phagocyte membrane-bound NADPH oxidase was studied using the luminol chemiluminescence (CL) response and the superoxide dismutase inhibitable reduction of ferricytochrome C. The NADPH oxidase was stimulated by phorbol myristate acetate (PMA). The results showed that high temperatures (39-43 degrees C) potentiate the AM inhibitory effect on CL peak response of phagocytes in a temperature-dependent manner. Furthermore, the inhibition of superoxide (O2-) production induced by AM was potentiated by incubating the cells at 39 or 43 degrees C at different time intervals. These studies suggest that high temperatures significantly potentiate the AM inhibitory effect on oxidative metabolism of PMNs in vitro. These actions of AM may influence the outcome in patients with infectious febrile conditions.
Insights
High temperatures enhance acetaminophen's inhibition of polymorphonuclear leukocyte (PMN) oxidative bursts. This potentiation of acetaminophen's effect on PMN metabolism may impact patients with infectious febrile conditions.
Area of Science:
- Immunology
- Pharmacology
- Biochemistry
Background:
- Acetaminophen is a common antipyretic and analgesic.
- Polymorphonuclear leukocytes (PMNs) are crucial immune cells involved in the oxidative respiratory burst to combat infections.
- Fever can alter drug efficacy and immune responses.
Purpose of the Study:
- To investigate the in vitro effect of elevated temperatures on acetaminophen-induced inhibition of PMN oxidative burst.
- To determine if hyperthermia potentiates acetaminophen's impact on phagocyte function.
Main Methods:
- Human whole blood or isolated PMNs were incubated with acetaminophen at temperatures of 39, 41, and 43 degrees C for varying durations.
- The oxidative respiratory burst was measured using luminol chemiluminescence (CL) and ferricytochrome C reduction assays.
- NADPH oxidase activity, stimulated by phorbol myristate acetate (PMA), was assessed.
Main Results:
- High temperatures (39-43 degrees C) significantly potentiated acetaminophen's inhibitory effect on the CL peak response of PMNs in a temperature-dependent manner.
- Acetaminophen-induced inhibition of superoxide (O2-) production was enhanced when cells were incubated at elevated temperatures (39 or 43 degrees C).
- The duration of incubation at high temperatures also influenced the potentiation of acetaminophen's inhibitory effects.
Conclusions:
- Elevated temperatures in vitro markedly potentiate the inhibitory effects of acetaminophen on the oxidative metabolism of PMNs.
- These findings suggest that fever may alter the immune-modulating actions of acetaminophen.
- The potentiated inhibition of PMN oxidative burst by acetaminophen at high temperatures could have implications for managing infectious febrile conditions.