Interestingly some drugs have been shown to be
Interestingly, some drugs have been shown to be effective in the regulation of cytokine production (such as IL-2, IL-10, IL-27, IL-35, IL-37 and transforming growth factor-β, TGF-β) and, therefore, having a key role in the management of certain inflammatory-based clinical conditions (Banchereau et al., 2012). The production of IL-10, an important cytokine that exerts potent immunosuppressive activity by downregulating monocytic cell and T cell activation, has been modulated by several monoterpenes (i.e. carvacrol and gamma-terpinene) in inflammatory conditions (Lima et al., 2013; Ramalho et al., 2016). The ability of IL-10 to inhibit pro-inflammatory cytokine production and its immune suppressive action can generates a cascade of beneficial effects in relation to conditions such as dysfunctional pain, rheumatoid arthritis, inflammatory bowel disease, psoriasis, organ transplantation, and chronic hepatitis C (Asadullah et al., 2003). Therefore, monoterpenes that stimulate IL-10 are promising drugs for the treatment of intractable diseases or those for which there is not a large therapeutic arsenal available.
Additionally, natural products have been shown to be a source of new substances with immunosuppressive activity that can reduce cytokine production by targeting the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, a strategic route for the management of cancer and other difficult to treat diseases (O\'Shea et al., 2005; Butturini et al., 2011). The JAK-STAT pathway plays a major role in the orchestration of the immune system, especially in relation to cytokine receptors. Despite this promising pharmacological profile, few studies have addressed this hypothesis of the mechanism of action at a molecular depth, meaning that treatments using this pathway remain little studied, particularly in relation to monoterpenes. This was corroborated by our review which shows an absence of studies with this approach (Table 1).
The future of new drugs that act on cytokines can be based on EHT 1864 of cytokines and their molecular pathways; natural products, such as monoterpenes, appear to be promising chemical entities with innovative mechanism of action for targeting different cytokines (Souza et al., 2014; Gandhi et al., 2018). In particular, monoterpenes which act on the cytokines TNF-α and IL-1β appear to be promising targets, as well as those that stimulate the production of anti-inflammatory cytokines such as IL-10, in the development of anti-inflammatory, analgesic and immunomodulator drugs. Thus, this review summarized the experimental evidence in order to highlight the major monoterpenes with the ability to modulate cytokines as a starting point for further clinical studies and the development of novel drugs.
Conclusion For more than a decade, many researchers have studied the effects of different monoterpenes on modulating the inflammatory cascade through in vivo and in vitro assays. The chemical characteristics and pharmacological properties of monoterpenes have been of interest to researchers, laboratories and pharmaceutical companies, with their anti-inflammatory and analgesic effects being identified as the most essential due to their abilities to modulate cytokines, act on important neurotransmitter systems responsible for generating and transmitting pain and their antioxidant profiles (Guimarães et al., 2013; Oliveira et al., 2017; Pina et al., 2017). In this review, we summarized the current knowledge on monoterpenes that possess anti-inflammatory effects and are able to modulate the release of anti-inflammatory and pro-inflammatory cytokines, as well as suggesting which monoterpenoid molecules are the most important in terms of an effective approach to treating inflammatory disease. This review described 24 monoterpenes that regulate cytokine release and the levels of others inflammatory mediators. Several different inflammatory markers were evaluated as a target of monoterpenes across the studies included within the review. The pro-inflammatory and anti-inflammatory cytokines found were TNF-α, IL-1β, IL-2, IL-5, IL-4, IL-6, IL-8, IL-10, IL-12 IL-13, IL-17A, IFNγ, TGF-β1 and IFN-γ. Given the numbers of cytokines measured in the studies, details are given in Table 1, Table 2.