Objectives: This study examined the plasma concentration of pro-inflammatory cytokine, interleukin 6 (IL-6), and anti-inflammatory cytokine, interleukin 10 (IL-10), in short-, and long-term opioid users with noncancer pain.
Materials and Methods: Adult patients with opioid therapy for noncancer pain were recruited from pain clinics at two tertiary hospital settings in Malaysia between February 2016 and March 2017. They were stratified into short- or long-term users based on opioid prescriptions ≥ 90 days per year. A 10mL blood sample was taken for the analysis of plasma concentrations of IL-6 and IL-10 and were quantified using a highly sensitive multiplex assay.
Results: Of 38 patients recruited, 24% (n = 9/38) and 76% (n = 29/38) were respectively short- and long-term opioid users. Short-term use of opioid was associated with higher levels of IL-6 (mean ± SD, 173.9 ± 13.7 pg/mL) and IL-10 (50 ± 5.8 pg/mL), whereas long-term use of opioids was associated with lower levels (no significant difference) of both cytokines IL6 (125 ± 16.1 pg/mL) and IL10 (41.3 ± 6.7 pg/mL). There was strong correlation between IL-6 and IL-10 within the same group (r² = 0.72, P < 0.05) and (r² = 0.76, P < 0.05) for short- and long-term users, respectively.
Conclusion: The duration of opioid use may modulate the level of pro-inflammatory cytokines in which it was higher in short-term use and lower in long-term use, but the effect of pain relief was similar as both cytokines were well correlated.
METHODS: Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model.
RESULTS: Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer.
CONCLUSION: Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.
MATERIALS AND METHODS: Six control and five DM Wistar rats were evaluated. DM was induced at 11 weeks of age using streptozotocin (STZ; 60 mg/kg, intraperitoneal). Animals were monitored up to 38 weeks of age, when plasma glucose, lipid profile, and markers specific for systemic inflammation, endothelial dysfunction, and oxidative stress were measured. The amount of fat within the aortic wall was assessed semiquantitatively using Oil Red O staining.
RESULTS: Diabetic rats presented significantly higher plasma glucose (p < 0.001), total cholesterol and triglycerides (both p = 0.02), high-sensitivity C-reactive protein (p = 0.01), and vascular endothelial growth factor (p = 0.04) levels, and significantly lower interleukin-10 (p = 0.04), superoxide dismutase (p < 0.01), and glutathione peroxidase (p = 0.01) levels than the control rats. Mild (grade 1) atherosclerotic lesions were observed in the aortic wall of 80% of the diabetic rats and in none of the control rats.
CONCLUSIONS: This study presents a STZ-induced type 1 DM rat model with one of the longest follow-ups in the literature. In this model, long-term DM created a highly pro-atherogenic environment characterised by hyperglycemia, dyslipidemia, systemic inflammation, endothelial dysfunction, and oxidative stress that resulted in the development of early aortic atherosclerotic lesions.
MATERIALS AND METHODS: In this cross-sectional study conducted over a 3-month period at a primary dental clinic in Malaysia, 45 participants were recruited via consecutive sampling and assigned into three groups, namely healthy periodontium group (n = 15), gingivitis group (n = 15), and periodontitis group (n = 15). Gingival crevicular fluid and plasma samples were collected from each participant. Enzyme-linked immunosorbent assay test was conducted to measure the concentration of IL-10, IL-17, IL-27, IL-35, and IL-37. Kruskal-Wallis H test was used to compare the interleukin levels between patient groups.
RESULTS: In GCF samples, IL-17 level was the highest in the periodontitis group (p <0.05), while IL-27 was the lowest (p <0.05). Meanwhile, plasma levels of IL-27 and IL-37 were significantly lower (p <0.05) in the periodontitis group, but plasma IL-35 levels were observed to rise with increasing disease severity.
CONCLUSION: There are reduced local and systemic levels of IL-27 in periodontitis patients.
CLINICAL SIGNIFICANCE: Periodontal diseases exert both local and systemic effects, resulting in the destruction of the tooth-supporting structures and contributing to the systemic inflammatory burden. Some of the cytokines that were investigated in the current study, IL-17, IL-27, IL-35, and IL-37, can be potential biomarkers that warrant further longitudinal clinical studies to determine their usefulness as prognostic/diagnostic markers.