Dataset Information

The Role of Interleukin 1β in the Pathogenesis of Lung Cancer.

ABSTRACT:

Introduction

Chronic inflammation is associated with an increased risk of several diseases, including cancer. A complex tumor microenvironment created and maintained by a range of cell types promotes tumor growth, angiogenesis, and metastasis. Inflammasomes, multicomplex cytosolic proteins, generate much of this inflammation, including the activation of the cytokine interleukin (IL)-1β. Inflammation generated by IL-1β is present in several disease states, including atherosclerosis, diabetes, and arthritis. IL-1β is activated when a specific inflammasome, nucleotide-binding domain-like receptor protein 3, induces cleavage of pro-IL-1β into its active form. Nucleotide-binding domain-like receptor protein 3 is up-regulated in lung cancer; IL-1β binds to its receptor and activates signaling pathways, including the MAPK, cyclooxygenase, and nuclear factor-κB pathways, leading to macrophage activation, intratumoral accumulation of immunosuppressive myeloid cells, and tumor growth, invasiveness, metastasis, and angiogenesis. Evidence suggests a role for IL-1β and some of its downstream effectors (e.g., IL-6, IL-8, C-reactive protein, cyclooxygenase-2) as prognostic markers in many malignancies, including lung cancer.

Methods

A phase III cardiovascular study of canakinumab, a human immunoglobulin Gk monoclonal antibody with high affinity and specificity for IL-1β, was conducted in patients who had a myocardial infarction.

Results

A subanalysis of this study found that treatment with canakinumab substantially reduced incident lung cancer and lung cancer mortality in a dose-dependent manner.

Conclusions

A phase III trial is currently recruiting participants to evaluate canakinumab as adjuvant treatment versus placebo in patients with lung cancer. Other studies are investigating combinations of established antineoplastic agents and canakinumab in both early- and advanced-stage NSCLC.

SUBMITTER: Garon EB

PROVIDER: S-EPMC8474414 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.