In summary the reduction of one or more pro
In summary, the reduction of one or more pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-8 was observed in almost all the monoterpenes studied. Increased levels of the anti-inflammatory cytokine IL-10 was shown to play a prominent function in the anti-inflammatory effect of monoterpenes, with this characteristics being more prevalent in alcohol monocyclic monoterpenes, such as α-terpineol, menthol and carvacrol. Downregulated production of proinflammatory cytokines and mediators, and up-regulated release of anti-inflammatory cytokines serve as key mechanisms in the management of inflammatory responses. Several anti-inflammatory molecules against pro-inflammatory cytokines such as IL-6 and TNF-α have already entered clinical trials as a potential treatments for inflammatory disorders (Reinhart and Karzai, 2001).
Furthermore, our survey provides evidence that NF-κB signaling is one of the most important pathways for the anti-inflammatory action of monoterpenes. The transcription factor NF-κB plays an important role in inflammation progression. Upon activation of the inflammation processes, NF-κB induces the sirtuins of many inflammatory genes, including COX-2 and iNOS which influences the expression of proinflammatory cytokines such as TNF-α, IL-1β, IL-6 and IL-8 which are crucial factors in the inflammatory process. Moreover, monoterpenes such as linalool, carvacrol, and D-limonene downregulate the NF-κB pathways, consequently inhibiting the expression of inflammatory mediators and suppressing the progression of inflammation.
Declarations of interest
Acknowledgments This study was financed in part by the Conselho Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq), the Fundação de Apoio à Pesquisa e a Inovação Tecnológica do Estado de Sergipe (Fapitec/SE) - Brasil, and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES - Finance Code 001).
Introduction A complex and dynamic immune activity is central to the success of human pregnancy , . The maternal immune system must maintain protection against infections, while keeping an immune balance and meeting the demands of the developing fetus. This challenge is reflected by an increased systemic level of inflammation in pregnancy, with elevated serum levels of C-reactive protein (CRP), cytokines like interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and oxidative stress markers such as oxidized low-density lipoprotein, compared to in the non-pregnant state , , , . Several pregnancy complications have been associated with further alterations of serum inflammatory markers, reflecting the detrimental role of a dysfunctional maternal immune response. How serum cytokine levels change during normal pregnancy is currently not well described, and characterizing the overall maternal immune status would be clinically useful , . Currently, CRP is the only inflammatory marker used in clinical practice in pregnancy. Cytokines are abundant at the maternal-fetal interface, and they are involved in regulating the delicate interaction between maternal and fetal cells. Studies in early pregnancy have focused on single cytokine measurements or the shift from inflammatory TH1 cytokines to more anti-inflammatory TH2 cytokines with advancing gestation , , , . The literature on cytokine development during normal pregnancy holds conflicting findings. Some studies report increasing TNF-α and interferon (IFN)-γ levels with gestational age , , , while others find no significant change , ,  or decreasing levels . These diverging results may imply that no single cytokine can explain the complex immunological network needed for maintaining a successful pregnancy, and a broader profiling of multiple cytokines is required. Powerful multivariate discriminating methods such as partial least squares discriminant analysis (PLS-DA) allows for analysis of several cytokines simultaneously while taking interactions between the cytokines into account. In this way, the complex maternal immune responses during pregnancy may be assessed for novel insight. We have recently demonstrated that broad maternal serum cytokine profiling at gestational age (GA) 11–13 weeks provided a sensitive measurement of maternal inflammatory status and could identify gestational hypertension occurring later in pregnancy .