Cytokine-modulating strategies and newer cytokine targets for arthritis therapy.

Existing Reviews

Please note, new claims can take a short while to show up.

No claims yet.

Annotation Summary

Term Occurence Count Dictionary
rheumatoid arthritis 3 rheumatologydiseases
synovitis 1 rheumatologydiseases
Etanercept 1 rheumatologydiseasesdrugs
Secukinumab 1 rheumatologydiseasesdrugs
Ustekinumab 1 rheumatologydiseasesdrugs
arthritis 45 rheumatologydiseases
autoimmune disease 4 rheumatologydiseases
infliximab 1 rheumatologydiseasesdrugs

Graph of close proximity drug and disease terms (within 200 characters).

Note: If this graph is empty, then there are no terms that meet the proximity constraint.

Review

Having read the paper, please pick a pair of statements from the paper to indicate that a drug and disease are related.

Select Drug Character Offset Drug Term Instance
Etanercept 8771 receptor[[30],[31]]Adalimumab aRecombinant IgG1 mAbBinds to TNFα and prevents it from activating TNF receptors[[32]] Etanercept aExtracellular domain of TNF receptor II (p75) and the Fc portion of IgG1 fusion proteinFunctions as
Secukinumab 8974 proteinFunctions as a decoy receptor to TNFα[[33]]Golimumab bHuman mAbNeutralizes TNFα bioactivity[[34]]IL-17 Secukinumab bHuman IgG1k mAbSelectively binds and neutralizes IL-17A[[35],[36]]Ixekizumab bHumanized IgG4 mAbNeutralizes
Ustekinumab 9187 mAbNeutralizes IL-17A[[37]]Brodalumab bHuman anti-IL17RA mAbInhibits the activity of IL-17[[38]]IL-12/IL-23 Ustekinumab bHuman IgG1κ mAbBlocks the biologic activity of IL-12 and IL-23 through their common p40 subunit by
infliximab 4947 TNFα has been instrumental in reducing the severity of arthritis, and a variety of biologics (e.g., infliximab , etanercept, etc.) based on this concept are currently being used in the clinic for the treatment of
Select Disease Character Offset Disease Term Instance
arthritis 635 (collection): 1/2015AbstractCytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as
arthritis 1082 damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA). For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by
arthritis 2050 IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis .1. IntroductionCytokines serve as the mediators of cellular differentiation, inflammation, immune pathology,
arthritis 3278 development and activation of osteoclasts, and the process of bone damage during the course of autoimmune arthritis [[1],[5]]. On the other hand, the classic anti-inflammatory cytokines include IL-4 and IL-10, which
arthritis 3499 immunosuppressive activities. IL-23 and IL-27 represent additional cytokines of interest in rheumatoid arthritis (RA). IL-23 exerts pro-inflammatory activity with its ability to expand Th17 cells [[6],[7]], whereas
arthritis 3981 salient features of three of the key pro-inflammatory cytokines (TNFα, IL-6, and IL-17) involved in arthritis are summarized below.TNFα is produced primarily by macrophages but also can be produced by other cells,
arthritis 4902 antibodies or the soluble decoy receptor for TNFα has been instrumental in reducing the severity of arthritis , and a variety of biologics (e.g., infliximab, etanercept, etc.) based on this concept are currently
arthritis 5122 used in the clinic for the treatment of RA (Table 1). IL-17 is a critical pro-inflammatory cytokine in arthritis pathogenesis. Six members of the IL-17 family are named IL-17A-F. Among these, IL-17A has dominant role
arthritis 5971 leading to bone and cartilage damage [[16],[17]]. The expression of IL-17A is increased in inflammatory arthritis [[16]], and neutralization of IL-17A has been shown to reduce the severity of arthritis in the CIA model
arthritis 6059 inflammatory arthritis [[16]], and neutralization of IL-17A has been shown to reduce the severity of arthritis in the CIA model of RA [[18]]. Antibodies against IL-17 are currently being investigated in clinical
arthritis 6245 investigated in clinical trials for the treatment of RA (Table 1).Figure 1The roles of cytokines in arthritis pathogenesis. The cytokine environment in the joints and the draining lymphoid tissue in rheumatoid
arthritis 6355 pathogenesis. The cytokine environment in the joints and the draining lymphoid tissue in rheumatoid arthritis is rather complex. There are multiple cell types that are present and each secretes a panel of pro-/anti-inflammatory
arthritis 7758 Th1, Th17, or Treg.ijms-16-00887-t001_Table 1Table 1Examples of antibodies tested for the treatment of arthritis and other inflammatory/autoimmune diseases.TargetAgentTypeMechanism of ActionRef.IL-1Anakinra aRecombinant
arthritis 9593 testing; and c completed or in preclinical testing.IL-6 has significant implications in the development of arthritis [[41]]. IL-6 is mainly produced by dendritic cells and macrophages. IL-6 triggers signaling by binding
arthritis 11468 this article, we describe a variety of approaches used for modulation of cytokine responses to control arthritis (Figure 2, Table 1 and Table 2) and the properties of relatively newer cytokines (IL-32, IL-34, and
arthritis 11671 IL-34, and IL-35), which have shown association with RA pathology and are being tested for their use in arthritis therapy in experimental models of RA.Figure 2Diverse strategies employed to control the activity of
arthritis 12952 properties under certain conditions.ijms-16-00887-t002_Table 2Table 2Cytokine modulation by gene therapy for arthritis therapy.Target CytokineVectorMode of Gene TransferModelRef.IL-1βrAAV-IL-1RaIn vivoMouse[[43]]IL-1Ra
arthritis 16444 to the controls [[60],[61]]. Similarly, the in vivo regulatory role of TNFR p55 in Yersinia-induced arthritis in mice has been reported [[62]]. In another study, the exposure of eye-derived antigen-presenting cell
arthritis 17123 with neutralizing antibodies against TNFα (described above) might unexpectedly show aggravation of arthritis . This may occur if TNFα neutralization is performed under conditions that otherwise facilitate anti-inflammatory
arthritis 17469 learn about the diverse functional attributes of these established cytokines in the pathogenesis of arthritis and other inflammatory disorders.A new therapeutic approach based on cytokine inhibition is represented
arthritis 19338 inhibitor. Rats/mice treated with this drug showed a marked reduction in the incidence and severity of arthritis in the adjuvant arthritis (AA) and collagen-induced arthritis (CIA) models of RA [[73]]. Multiple phase
arthritis 19364 with this drug showed a marked reduction in the incidence and severity of arthritis in the adjuvant arthritis (AA) and collagen-induced arthritis (CIA) models of RA [[73]]. Multiple phase III trials have been conducted
arthritis 19400 reduction in the incidence and severity of arthritis in the adjuvant arthritis (AA) and collagen-induced arthritis (CIA) models of RA [[73]]. Multiple phase III trials have been conducted using Tofacitinib in RA patients
arthritis 21488 the knee joint of rats was effective in producing optimal level of IL-1Ra locally and in suppressing arthritis in LPS-induced arthritis model. The IL-1Ra-encoding gene was among the first ones to be tested for potential
arthritis 21513 effective in producing optimal level of IL-1Ra locally and in suppressing arthritis in LPS-induced arthritis model. The IL-1Ra-encoding gene was among the first ones to be tested for potential use in a gene therapy
arthritis 22554 histological signs of the disease [[46]]. In another study in CIA, a similar treatment reduced clinical arthritis as well as IL-1β and IL-12 in the paws [[47]]. In a study in RA patients, the TNFα gene delivered
arthritis 23220 IFN-βIFN-β possesses significant immunomodulatory properties and this cytokine has been considered for arthritis therapy [[49],[89]]. Systemic administration of IFN-β was effective in suppressing arthritis in mice
arthritis 23314 considered for arthritis therapy [[49],[89]]. Systemic administration of IFN-β was effective in suppressing arthritis in mice and monkeys, but did not have much effect in RA patients [[89]]. Therefore, approaches using
arthritis 23615 adenovirus-mediated gene transfer into the ankle joints of rats with AA resulted in the inhibition of arthritis progression and protection against bone damage [[49]].4.5. IL-4 and IL-10Gene therapy approaches using
arthritis 23785 IL-4 and IL-10Gene therapy approaches using anti-inflammatory cytokines have also been attempted for arthritis control. Injection of an adenoviral vector encoding the gene for human IL-4 into mice resulted in decreased
arthritis 24215 knee joints of mice resulted in reduced synovitis and cartilage proteoglycan depletion in experimental arthritis [[51]].4.6. Small Interfering RNA (SiRNA)/Short Hairpin RNA (ShRNA)-Induced Cytokine Modulation for
arthritis 24902 systemically administered into mice with CIA. It resulted in significant reduction in the severity of arthritis as well as TNFα mRNA level in the joints [[91]]. The siRNA thus delivered was targeted primarily to
arthritis 25223 arginine-glycine-aspartate (RGD) peptide and encapsulating STAT1-targeting siRNAs were effective in suppressing arthritis via selective inhibition of macrophage and dendritic cell activation [[92]]. Examination of the paws
arthritis 25429 paws revealed reduced mRNA for STAT1 but increased mRNA for IL-10, an immunomodulatory cytokine for arthritis . In another study, the T-bet shRNA recombinant plasmid (p-T-shRNA), which was aimed at inhibiting T-bet,
arthritis 25941 target-independent suppression and off-target effects [[94],[95]].Additional approaches for gene therapy of arthritis have been explored, including antigen-induced tolerance [[96],[97]]. Application of gene therapy to
arthritis 26141 therapy to modulation of cytokines offers a new approach for the management of RA and other types of arthritis . Despite several notable advancements discussed above, the goal of using gene therapy for effective
arthritis 27925 pose some risks, with new advancements and ethical regulations, it can be harnessed for treatment of arthritis and other chronic, debilitating diseases.5. The Relatively Newer Cytokines (IL-32, IL-34 and IL-35)
arthritis 31794 disease-aggravating effect of IL-35. In that study, IL-35 gene transfer resulted in aggravation of arthritis (CIA) and increased the ratio of Th17/Treg cells in the spleen of arthritic mice [[124]]. Studies in
arthritis 32372 as IL-32, IL-34 and IL-35 are being investigated for their role in the pathogenesis and treatment of arthritis . The predominantly pro-inflammatory members of this group can be targeted for their downmodulation,
arthritis 32595 predominantly anti-inflammatory members of the group can be boosted for their therapeutic effects in arthritis . Various approaches, including antibody neutralization, gene therapy, transcriptional silencing, etc.,
arthritis 32970 approaches coupled with novel cytokine targets will have a significant impact on the management of arthritis in the very near future.6. ConclusionsPro-inflammatory cytokines, which drive the initiation and progression
arthritis 33103 future.6. ConclusionsPro-inflammatory cytokines, which drive the initiation and progression of autoimmune arthritis , are the prime therapeutic targets for this debilitating disease. The biologics based on neutralization
arthritis 33691 anti-inflammatory. It is hoped that one or more of these cytokine might offer a viable therapeutic target for arthritis therapy. Overall, most of the effort in cytokine-based therapy is focused on dampening pro-inflammatory
arthritis 33947 promising leads for accentuation of the anti-inflammatory/immunoregulatory cytokines to control autoimmune arthritis . In conclusion, there is high optimism for the development of new arthritis therapies based on advances
arthritis 34023 cytokines to control autoimmune arthritis. In conclusion, there is high optimism for the development of new arthritis therapies based on advances in basic science aspects of this disease in the coming years
autoimmune disease 7791 Treg.ijms-16-00887-t001_Table 1Table 1Examples of antibodies tested for the treatment of arthritis and other inflammatory/ autoimmune disease s.TargetAgentTypeMechanism of ActionRef.IL-1Anakinra aRecombinant IL-1RαPrevents binding of IL-1β to
autoimmune disease 11931 Pro-inflammatory cytokines, when produced in excess, can cause significant damage to tissues in various autoimmune disease s. Multiple approaches have been developed to prevent and ameliorate the harmful side effects of the
autoimmune disease 13963 a particular pathogenic cytokine offers a distinct advantage for the treatment of RA and some other autoimmune disease s. The main target cytokines of interest for the treatment of RA are: TNFα, IL-1β, IL-6, IL-17, and
autoimmune disease 14679 mechanisms of actions of different biologics that have been used for the treatment of RA and some other autoimmune disease s are summarized in Table 1.Although efficacious, the above-mentioned biologics have some limitations
rheumatoid arthritis 1071 and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA). For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by
rheumatoid arthritis 3488 display immunosuppressive activities. IL-23 and IL-27 represent additional cytokines of interest in rheumatoid arthritis (RA). IL-23 exerts pro-inflammatory activity with its ability to expand Th17 cells [[6],[7]], whereas
rheumatoid arthritis 6344 arthritis pathogenesis. The cytokine environment in the joints and the draining lymphoid tissue in rheumatoid arthritis is rather complex. There are multiple cell types that are present and each secretes a panel of pro-/anti-inflammatory
synovitis 24152 inflammation-dependent promoters such as Saa3 and Mmp13 intra-articularly into knee joints of mice resulted in reduced synovitis and cartilage proteoglycan depletion in experimental arthritis [[51]].4.6. Small Interfering RNA (SiRNA)/Short

You must be authorized to submit a review.