Targeting lymphocyte Kv1.3-channels to suppress cytokine storm in severe COVID-19: Can it be a novel therapeutic strategy?

Kazama, Itsuro

doi:10.5582/ddt.2020.03046

Cited by 20 publications

(20 citation statements)

References 17 publications

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“…Exorbitant inflammation evokes a serious of expanded cascade reaction, leading to systemic inflammation and multiple organ dysfunction syndromes [ 9 , 36 ]. Other research groups have revealed that cytokine storm is observed in COVID-19 patients and inflammation suppression alleviated the severity of COVID-19 [ 37 , 38 ]. In our present research, IL-17 was also shown to be prominently and positively related with inflammatory cytokines in CAP patients.…”

Section: Discussionmentioning

confidence: 99%

Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study

Chen

Wang

et al. 2021

BMC Pulm Med

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Background Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study. Methods All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II. Results Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively. Conclusions Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.

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Section: Discussionmentioning

confidence: 99%

Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study

Chen

Wang

et al. 2021

BMC Pulm Med

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“…Chloroquine has been in use as an antimalarial agent for over 5 decades. It also suppresses the activity of mammalian delayed rectifier K + channels (Kv1.3) in leukocytes and lymphocyte production of pro-inflammatory cytokines ( 58 ). Chloroquine has anti-inflammatory and immunomodulatory properties and is used to treat autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosus.…”

Section: Ion Channel Blockers With Potential As Anti-tuberculosis Agentsmentioning

confidence: 99%

Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents

et al. 2021

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Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of multi-drug regimens and is complicated by problems of compliance and drug resistance. While most Mycobacterium tuberculosis (Mtb) bacilli are quickly killed by the drugs, the prolonged course of treatment is required to clear persistent drug-tolerant subpopulations. Mtb’s differential sensitivity to drugs is, at least in part, determined by the interaction between the bacilli and different host macrophage populations. Therefore, to design better treatment regimens for TB, we need to understand and modulate the heterogeneity and divergent responses that Mtb bacilli exhibit within macrophages. However, developing drugs de-novo is a long and expensive process. An alternative approach to expedite the development of new TB treatments is to repurpose existing drugs that were developed for other therapeutic purposes if they also possess anti-tuberculosis activity. There is growing interest in the use of immune modulators to supplement current anti-TB drugs by enhancing the host’s antimycobacterial responses. Ion channel blocking agents are among the most promising of the host-directed therapeutics. Some ion channel blockers also interfere with the activity of mycobacterial efflux pumps. In this review, we discuss some of the ion channel blockers that have shown promise as potential anti-TB agents.

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“…For the development of idiopathic pulmonary fibrosis, several growth factors, such as transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and epidermal growth factor (EGF), are generally considered to be responsible (7,8), since these growth factors promote the profibrogenic process of the lung after injury. For the development of "post-COVID-19" pulmonary fibrosis, cytokine storm, which is characterized by the over-activation of leukocytes and the uncontrolled secretion of proinflammatory cytokines, is additionally thought to be responsible (9,10). These cytokines impair the recovery process from the lung injury and stimulate the activity of fibroblasts to produce collagen, and thus promote the progression of pulmonary fibrosis (11).…”

Section: Itsuro Kazama *mentioning

confidence: 99%

“…Taking into account such pharmacological properties of these drugs, they may also be useful in the treatment of post-COVID-19 pulmonary fibrosis, in addition to their usefulness in suppressing cytokine storm (9).…”

Section: Itsuro Kazama *mentioning

confidence: 99%

Targeting lymphocyte Kv1.3-channels to suppress cytokine storm in severe COVID-19: Can it be a novel therapeutic strategy?

Cited by 20 publications

References 17 publications

Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study

Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study

Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents

Stabilizing mast cells by commonly used drugs: a novel therapeutic target to relieve post-COVID syndrome?

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