Thymulin, free or bound to PBCA nanoparticles, protects mice against chronic septic inflammation

• Published in: PloS one Vol. 13; no. 5; p. e0197601
• Main Authors: Novoselova, Elena G, Lunin, Sergey M, Glushkova, Olga V, Khrenov, Maxim O, Parfenyuk, Svetlana B, Zakharova, Nadezhda M, Fesenko, Evgeny E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.05.2018; Public Library of Science (PLoS)
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Antioxidants; Apoptosis; Biology and Life Sciences; Biomarkers; Biophysics; Blood; Body Temperature; Brain; Brain - metabolism; Cell number; Cytokines; Cytokines - blood; Disease Models, Animal; Enbucrilate - chemistry; Engineering and Technology; Fever; Gene Expression; Heat shock proteins; Hsp72 protein; Hsp90 protein; Immune system; Infections; Inflammation; Kinases; Lipopolysaccharides; Lipopolysaccharides - adverse effects; Lipopolysaccharides - immunology; Male; MAP kinase; Medicine and Health Sciences; Melatonin; Mice; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; NF-κB protein; Oxidative stress; Particle Size; Pathways; Patients; Peptides; Protein kinase C; Proteins; Sepsis; Sepsis - blood; Sepsis - drug therapy; Sepsis - etiology; Sepsis - metabolism; Serotonin; Signal Transduction; Signaling; Spleen; Spleen - cytology; Thymic Factor, Circulating - chemistry; Thymic Factor, Circulating - pharmacology; Thymic hormones; TLR4 protein; Toll-like receptors; Transcription factors; Tumor necrosis factor-TNF; Russia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0197601

In the present work, we aimed to study the effects of free and polybutylcyanoacrylate nanoparticle-bound thymulin on immune cell activity in mice with chronic inflammation. NF-κB, MAPK, and PKC-θ signaling pathway activity was assessed, alongside Hsp72, Hsp90-α, and TLR4 expression and levels of apoptosis. In addition, plasma cytokines and blood and brain melatonin and serotonin levels were measured. In mice treated with gradually raised doses of lipopolysaccharide, significant increases in the activity of the signaling pathways tested, heat-shock protein and TLR4 expression, lymphocyte apoptosis, and plasma proinflammatory cytokine levels were noted. Moreover, we observed significantly heightened serotonin concentrations in the plasma and especially the brains of mice with inflammation. In contrast, melatonin levels were reduced in the tissues examined, particularly so in the brain. Treatment of these mice with thymulin alleviated fever, reduced apoptosis, increased splenic cell number, and decreased cytokine production, Hsp72, Hsp90, and TLR4 expression, and the activity of the signaling pathways examined. In addition, thymulin partially restored brain and blood serotonin and melatonin levels. Thus, thymulin suppressed the proinflammatory response in LPS-treated mice, indicating the potential of thymulin co-therapy in the treatment of sepsis. Nanoparticle-bound thymulin was more effective in several respects.