The aim of the study: to reveal peculiarities of the phagocytic activity of TLR4, TLR7/8-activated monocytes of peripheral blood, depending on the type of multiple sclerosis and clinical effectiveness of the treatment. Material and methods. E. coli or ssRNA40/LyoVec lipopolysaccharide as TLR4 and TLR7/8 agonists were added to the monocyte-enriched cell suspension, respectively, and incubated for 24 hours at t 37 °C under an atmosphere of 5 % CO 2. In parallel series, ram erythrocytes (RE) sensitized with hemolytic serum and inactivated C. albicans cells were used as phagocytosis objects; the incubation time was 30 minutes. The phagocytic index was calculated as the percentage of phagocytic monocytes and the phagocytic number as the ratio of the total number of absorbed REs or C. albicans cells to the number of monocytes that entered into phagocytosis. The study presents the results of examination of 58 patients with recurring remitting (RRMS) and 36 patients with progressive (PMS) multiple sclerosis. Results. The differences in the activation mechanisms of peripheral blood monocytes in patients with PC, which consist in different phagocytic activity in response to stimulation of TLR4 and TLR 7/8 depending on the disease conditions, were presented. Phagocytic activity lesions of monocytes were observed both in patients with RRMS and PMS, associated mainly with FcR-mediated mechanisms of phagocytosis. IFN-β therapy in patients with RRMS led to the correction of such disorders in patients with high treatment efficacy (responders), and TLR7/8-mediated activation of monocytes was accompanied by an increase in the number of phagocytic cells. In patients with low efficacy of IFN-β therapy (nonresponders), the nature of changes in the phagocytic activity of stimulated monocytes indicated a decrease in the functional reserve with regard to FcR-mediated phagocytosis. Conclusions. The obtained results indicate differences in phagocytic activity indices during stimulation of TLR4 and TLR7/8 and may indicate the presence of functional and phenotypic alterations of peripheral blood monocytes depending on the effectiveness of MS treatment.
The relationships between the nature of the prognosis, normal and elevated levels of pro-inflammatory (INF-γ, IL-1β) and anti-inflammatory cytokines (IL-10, IL-12), the prevalence of haplotypes AA and AG in 105 patients with sporadic form (recurrent course (RС) — 72, progressive types of course (PTС) — 33) and in 33 patients with family form (RС — 15, PTС — 18) of multiple sclerosis. Studies have shown that with RС, a favorable and uncertain prognosis in patients with a sporadic form of MS was significantly more likely to occur with a normal level of anti-inflammatory cytokines (IL-10, IL-12), while in a familial form, a normal level of IL-10 was associated with a favorable and IL-12 — with an uncertain forecast. With PTС in patients with a sporadic form, the normal INF-γ content was more likely to occur with an unfavorable prognosis, while its increased content was characteristic of an uncertain prognosis. In the family form, an unfavorable prognosis was more common with an elevated level of the pro-inflammatory cytokine INF-γ and a normal level of anti-inflammatory cytokine IL-10. This suggests that a complex and differentiated interaction of pro- and anti-inflammatory cytokines occurs with the participation of various pathogenetic mechanisms for different forms and types of course. Uncertain prognosis in familial form of RT, unlike sporadic, was more common in patients with AA haplotype. A comparative assessment of the relationship between AA and AG haplotypes revealed the predominance of AA haplotype with an uncertain prognosis in patients with familial form of RT. Haplotype AG was significantly more common in the family form of PTT and did not depend on the nature of the prognosis. Thus, the prevalence of AA and AG haplotypes in both sporadic and familial forms revealed a close relationship with the nature of the prognosis and the type of course. Key words: multiple sclerosis, sporadic and familial form, prognosis, type of course, cytokines, haplotype
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.