The effect ofin vitro andin vivo dexamethasone on human neutrophil function

Abstract

There is a significant fall in PMN chemotaxis to the peptide FMLP in response to increasing concentrations of dexamethasone in vitro. The response fell in a dose related manner from a control value of 53.7 SE +/- 9.6 cells per high power field (cpf) to 47.3 SE +/- 8.1 at 10(-6) M (p less than 0.05) and 24.7 +/- 8.9 at 10(-3) M (p less than 0.025). A similar response was observed for the chemoattractants zymosan activated serum and the sol phase of purulent sputum. The effect was independent of protein synthesis or the period of incubation. Twelve milligrams of dexamethasone taken daily by 6 healthy volunteers resulted in a significant (p less than 0.025) reduction in the chemotactic response of PMN to 10(-8) M FMLP (from 29.5 +/- 1.55 to 13.7 +/- 1.8 cpf) which was apparent within 2 hours of taking the first dose. This effect was sustained for the three days on which dexamethasone was taken but returned to normal 7 days after the last dose had been administered. Dexamethasone therapy had no effect on unstimulated PMN superoxide anion production either in vitro or in vivo. The in vivo effect on neutrophil function occurred at mean serum dexamethasone concentrations of 1.26 (+/- 0.28) X 10(-7) M on day 1, 1.44 (+/- 0.15) X 10(-7) M on day 2 and 1.31 (+/- 0.13) X 10(-7) M on day 3. Thus we conclude that dexamethasone concentration which inhibit PMN chemotaxis in vivo are much lower than those required to exert the same effect in vitro.

In Vitro Antichemotactic Activity of Chamomilla recutita Hydroethanol Extract

“…Our results showed a significant inhibitory effect of chamomile extract upon casein-induced leukocyte chemotaxis, which was close to the significant effects caused by DEXA, an anti-inflammatory drug commonly used in this system as a negative regulator of leukocyte chemotaxis (Lomas et al, 1991;Zentay et al, 1999). Moreover, the independent pretreatment of these cells with morphine or naloxone before their exposure to the plant extract reduced this activity.…”

“…For DEXA, which has the ability to inhibit the migration properties of leukocytes in vitro (Lomas et al, 1991;Zentay et al, 1999) and has been considered as a model for this purpose, the value found using similar conditions was 69.1 AE 6.2% (n ¼ 17; p 0.005, when compared with the control group). Figure 2 depicts the results of pretreating human leukocytes with morphine or naloxone before chemotaxis toward casein gradient.…”

Comparison of chemical constituents of Chamomilla recutita (L.) rauschert essential oil and its anti-chemotactic activity

“…For the local chamomile extract, the maximum inhibition effect observed was at the concentration of at least one hundred times higher than the value found for the imported sample under the experimental conditions used. Moreover, both effects were very close to the significant effects caused by DEXA, an anti-inflammatory drug commonly used in this system as a negative regulator of leukocyte chemotaxis (Lomas et al, 1991;Zentay et al, 1999). These results could reflect the differences in their composition, some of which were revealed by the GC-MS analysis performed in this work.…”

“…The maximum significant effect was at the concentration of 0.1 µg/ml of extract, the lowest dose tested, with only 65.9 ± 4.3% of the cells recovered from the lower compartment (n = 8; p ≤ 0.005). For DEXA (10 -5 M), which had the ability to inhibit the migration properties of leukocytes in vitro (Lomas et al, 1991;Zentay et al, 1999), and had been considered a model for this purpose, the value found using similar conditions was 69.1 ± 6.2% (n = 17; p ≤ 0.005). M) or with the Brazilian ( ) or the Egyptian ( ) chamomile extract at the indicated concentrations, and induced to migrate towards 1% casein gradient, for 90 min at 37°C, in a Boyden system in which the compartments were separated by a 5 µm pore size polycarbonate filter.…”

Oxidative Stress in Chronic Obstructive Pulmonary Disease

“…In another study, 0¿" generation by PMN was decreased after in vivo prednisolone treatment in patients with emphysema (257). In another study, dexamethasone did not alter unstimulated O f production by PMN either in vitro or in vivo (258). Likewise, inhaled corticosteroids did not change PMN numbers or IL-8 levels in the peripheral blood but did decrease the number of PMN in the sputum of COPD patients (259).…”