TY - JOUR
T1 - Investigation of Correlation between Resistance to Diazepam and Expression of Inflammatory Markers in The Peripheral Blood of Patients with Status Epilepticus
AU - Mahama, Corry Novita
AU - Louisa, Melva
AU - Octaviana, Fitri
AU - Suryandari, Dwi Anita
AU - Budikayanti, Astri
AU - Wibowo, Heri
N1 - Publisher Copyright:
© 2023 Mahama et al.
PY - 2023/12
Y1 - 2023/12
N2 - Objective. This study investigated several inflammatory markers’ gene and protein expression in status epilepticus (SE) and their correlation with diazepam resistance. Materials and Methods. Peripheral blood samples were collected from 18 adult patients with SE in Cipto Mangunkusumo Central Hospital, consisting of 12 diazepam-responsive and six diazepam-resistant samples, within 72 hours of the onset of the seizure. We collected baseline demographic and clinical data from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, stimulated with lipopolysaccharide (LPS) 1 mg/ml, and harvested for RNA isolation. The RNA was used to determine the expression of Human Mobility Group Box 1 (HMGB1), Interleukin-6 (IL-6), IL-10, Toll-like Receptor 4 (TLR4), and Glial fibrillary acidic protein (GFAP). In addition, we performed serum protein assay of HMGB1, IL-6, IL-10, TLR4, and GFAP to compare with gene expression. Results. We found a significant difference between the responsive and resistant groups for serum HMGB1 and IL-6 concentration. The mRNA expression of HMGB1 and IL-6 was significantly higher in LPS-stimulated samples in the responsive but not in the resistant groups. The ratio of IL-6 to IL-10 showed a significant difference between LPS and control in the responsive group. Diazepam response was significantly correlated with seizure duration and serum protein concentration of HMGB1. Conclusion. HMGB1 was highly expressed in the resistant group and strongly correlated with diazepam response, and there was a significant increase in HMGB1 mRNA expression in response to LPS stimulation. These findings suggest that targeting HMGB1 may be a promising therapeutic strategy and that HMGB1 levels could be a valuable biomarker for predicting diazepam resistance in SE.
AB - Objective. This study investigated several inflammatory markers’ gene and protein expression in status epilepticus (SE) and their correlation with diazepam resistance. Materials and Methods. Peripheral blood samples were collected from 18 adult patients with SE in Cipto Mangunkusumo Central Hospital, consisting of 12 diazepam-responsive and six diazepam-resistant samples, within 72 hours of the onset of the seizure. We collected baseline demographic and clinical data from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, stimulated with lipopolysaccharide (LPS) 1 mg/ml, and harvested for RNA isolation. The RNA was used to determine the expression of Human Mobility Group Box 1 (HMGB1), Interleukin-6 (IL-6), IL-10, Toll-like Receptor 4 (TLR4), and Glial fibrillary acidic protein (GFAP). In addition, we performed serum protein assay of HMGB1, IL-6, IL-10, TLR4, and GFAP to compare with gene expression. Results. We found a significant difference between the responsive and resistant groups for serum HMGB1 and IL-6 concentration. The mRNA expression of HMGB1 and IL-6 was significantly higher in LPS-stimulated samples in the responsive but not in the resistant groups. The ratio of IL-6 to IL-10 showed a significant difference between LPS and control in the responsive group. Diazepam response was significantly correlated with seizure duration and serum protein concentration of HMGB1. Conclusion. HMGB1 was highly expressed in the resistant group and strongly correlated with diazepam response, and there was a significant increase in HMGB1 mRNA expression in response to LPS stimulation. These findings suggest that targeting HMGB1 may be a promising therapeutic strategy and that HMGB1 levels could be a valuable biomarker for predicting diazepam resistance in SE.
KW - Diazepam Resistance
KW - GFAP
KW - HMGB1
KW - Interleukin
KW - Status Epilepticus
KW - TLR4
UR - http://www.scopus.com/inward/record.url?scp=85185926076&partnerID=8YFLogxK
U2 - 10.5644/ama2006-124.423
DO - 10.5644/ama2006-124.423
M3 - Article
C2 - 38407083
AN - SCOPUS:85185926076
SN - 1840-1848
VL - 52
SP - 169
EP - 181
JO - Acta medica academica
JF - Acta medica academica
IS - 3
ER -