The impact of tocilizumab treatment on the severity of inflammation and survival rates in sepsis is significantly influence by the timing of administration.
Taha Tavaci, Zekai Halici, Elif Cadirci, Mustafa Ozkaraca, Kamber Kasali
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引用次数: 0
Abstract
Background: Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection. Due to the high mortality rates and treatment costs associated with sepsis, research is focusing on innovative treatment strategies to replace one dimensional approaches. Recent studies are being conducted on the use of immunotherapeutics in sepsis and the impact of treatment timing. This study aimed to elucidate the significance of treatment timing in sepsis immunotherapy with Tocilizumab (TCZ) and the implications of differences in treatment timing.
Methods: LPS-induced sepsis model was established in rats to assess the changes in interleukin-6 (IL-6) over a 24-h sepsis period and its correlation with lung and kidney injury. The impact of TCZ treatments at various time points was evaluated by molecular and histopathological methods. The effect of TCZ treatment timing on survival was analyzed using Kaplan-Meier survival analysis.
Results: IL-6 reached peak concentrations in the early stages of sepsis, whereas lung damage peaked subsequent to the IL-6 peak, and kidney damage manifested considerably later. The early treatment group, receiving intervention one hour post-sepsis induction, exhibited the most favorable molecular and histopathological outcomes. Conversely, the group receiving the latest treatment, at sixteen hours post-sepsis induction, demonstrated the poorest results. Survival analysis indicated that the group treated at the tenth hour exhibited the highest survival rate.
Conclusion: Variations in the timing of sepsis treatment with TCZ yield significantly different molecular outcomes, histopathological results, and survival rates. A thorough investigation of the timing of immunotherapeutic applications in sepsis treatment will enhance the efficiency of sepsis treatments.
期刊介绍:
Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas:
-Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states
-Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs
-Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents
-Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain
-Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs
-Muscle-immune interactions during inflammation [...]