Inhibition of Prostaglandin Biosynthesis in Human Endotoxin-Stimulated Peripheral Blood Monocytes: Effects of Caffeine

Abstract

There is an ongoing debate about possible advantages of the coadministration of caffeine with cyclooxygenase (COX) inhibitors in the treatment of pain. There are results suggesting interference by caffeine with COX expression and activity in rat immune cells. In the present study, we have used, therefore, human endotoxin-stimulated monocytes to investigate a possible influence of caffeine on indometacin-induced inhibition of prostaglandin E₂ (PGE₂) formation. Endotoxin caused a concentration- and time-dependent increase in immunoreactive PGE₂ that was dependent on CD14-mediated mechanisms. In order to investigate pharmacological inhibition of the COX activity, a submaximal concentration of 1 ng/ml endotoxin (4 h exposure time) was used. Indometacin caused a concentration-dependent inhibition of PGE₂ with an apparent IC₅₀ of 8.9 ± 1.4 × 10^–9 mol/l and an I_max of 1 x 10^–7 mol/l. Caffeine (5 × 10^–6 to 1.5 × 10^–4 mol/l) on its own produced no statistically significant effect on endotoxin-induced PGE₂ formation. In the presence of caffeine (5 × 10^–6 to 1.5 × 10^–4 mol/l), inhibition of PGE₂ biosynthesis by indometacin (1 × 10^–8 mol/l) was not significantly altered. These results show that, in human monocytes, caffeine, up to concentrations severalfold higher than those reached in patients, has no significant effect on endotoxin-induced PGE₂ formation nor on its inhibition by indometacin.

Adjuvant effect of caffeine on acetylsalicylic acid anti‐nociception: Prostaglandin E2 synthesis determination in carrageenan‐induced peripheral inflammation in rat

“…These results are in agreement with those presented ''in vitro'' by Engelhardt et al (1997) and Ulcar et al (2003), where CAF was associated with ASA and indometacin, respectively. As expected, ASA showed a D-R relationship on the inhibition of PGE-2 synthesis.…”

“…On the other hand, neither CAF on its own (5 mg/kg) altered PGE-2 levels when compared with control animals, nor enhanced the effect of ASA when administered in combination. These results are in agreement with those presented ''in vitro'' by Engelhardt et al (1997) and Ulcar et al (2003), where CAF was associated with ASA and indometacin, respectively. On the opposite, Fiebich et al (2000), not only reported an inhibitory effect of CAF alone, but also an adjuvant effect on COX-2 activity and PGE-2 synthesis in rat microglial cells.…”

Monocytes and Macrophages Serve as Potent Prostaglandin D2 Sources during Acute, Non-Allergic Pulmonary Inflammation

“…As neutrophils are present in great numbers during acute inflammation, we additionally investigated PGD 2 production by human peripheral blood neutrophils; however, circulatory neutrophils neither expressed relevant levels of hPGDS, nor released PGD 2 after LPS stimulation ( Figure S5 ). Previously, we have shown that primary human monocytes release PGE 2 after LPS/IFN-γ stimulation [ 20 , 29 ]. In line with this, we observed a steady increase in PGE 2 levels within 48 h that exceeded PGD 2 levels at all time points ( Figure 5 D,E).…”

A Straightforward Approach towards Antibacterial and Anti‐Inflammatory Multifunctional Nanofiber Membranes with Sustained Drug Release Profiles

“…[20][21][22][23] Notably, indomethacin (Indo), which exerts its anti-inflammatory effect by inhibiting the production of prostaglandins (PGs), is an NSAID with very effective antipyretic, analgesic, and antiinflammatory activity, and fewer side effects and higher safety compared with corticosteroids. [24,25] In order to enhance the anti-inflammatory ability of wound dressings, Indo is often selected to be incorporated in situ into nanofiber membranes, such as polyvinylpyrrolidone-Indo nanofiber membrane (Rasekh et al) [26] and corn protein zein-hydrophobic ethyl cellulose-Indo composite nanofiber membrane (Lu et al). [27] In fact, nanofiber membranes merely loaded with anti-inflammatory drugs seem to be unsatisfactory to meet practical requirements.…”