Interleukin-32: its role in asthma and potential as a therapeutic agent

Abstract

Interleukin (IL)-32, also named natural killer cell transcript 4 (NK4), has increasingly been described as an immunoregulator that controls cell differentiation and cell death and is involved in the stimulation of anti−/pro-inflammatory cytokines. Abnormal presence of IL-32 has been repeatedly noticed during the pathogenesis of allergic, infectious, cancerous, and inflammatory diseases. Of particular note was the observation of the anti-inflammatory property of IL-32 in a murine ovalbumin model of allergic asthma. Compared to wild-type mice, IL-32γ transgenic mice show decreased levels of inflammatory cells, recruited eosinophils, and lymphocytes in bronchoalveolar lavage fluid in a mouse model of acute asthma. To date, the molecular mechanism underlying the role of IL-32 in asthma remains to be elucidated. This review aims to summarize recent advances in the pathophysiology of asthma and describe the links to IL-32. The possibilities of using IL-32 as an airway inflammation biomarker and an asthma therapeutic agent are also evaluated.

Increased levels of interleukin‐32 isoforms alpha, beta, gamma, and delta in the gingival crevicular fluid and plasma of the patients with periodontitis

“…In accordance with these studies, we have determined in our previous animal and human studies that IL‐32 levels increased in periodontal disease status and showed positive correlation with TNF‐α and IL‐6 28,46 . On the other hand, it has been stated that IL‐32 may restrict the generation of pro‐inflammatory factors 13 . Hence, few studies investigating the effect of IL‐32 on periodontal disease have conflicting evidence that detects IL‐32 levels in different samples as increased or decreased 26‐28 .…”

“…Hence, few studies investigating the effect of IL‐32 on periodontal disease have conflicting evidence that detects IL‐32 levels in different samples as increased or decreased 26‐28 . This discrepancy might be explained either by the functional differences among IL‐32 isoforms that can encourage either pro‐ or anti‐inflammatory milieu or various dynamic processes of the periodontal disease's circumstances 13,14,24 . In studies that have evaluated IL‐32 levels in various diseases to date, it has been stated that IL‐32 isoforms are not evaluated as common limitations and it has been suggested that the function of each isoform may have a different effect 7,28,43,44 …”

“…To date, it has been described that IL‐32 has nine distinct isoforms including IL‐32α, IL‐32β, IL‐32γ, IL‐32δ, IL‐32ε, IL‐32ζ, IL‐32η, IL‐32θ, and IL‐32 small (sm)3 10‐12 . The role of IL‐32 in inflammation is pleiotropic, because it is related with the enhancing both pro‐inflammatory and anti‐inflammatory cytokines 13,14 . It is stated that this property is due to its isoforms having different biological activities and properties 13,15 .…”

Early Detection of Peripheral Blood Cell Signature in Children Developing β-Cell Autoimmunity at a Young Age

“…Nonetheless, human IL32g transgenic mice exhibit impaired glucose tolerance and increased levels of IFNg and other proinflammatory cytokines in the pancreas, as well as accelerated streptozotocininduced experimental T1D (52). No specific cell-surface receptor for IL32 has been identified, but it may act through cell-surface integrins or proteinase-3 (53).…”

The role of Interleukin‐32 in autoimmunity

“…A growing body of evidence implicates IL‐32 in health and disease. Its roles in host responses to pathogens 3,4 allergy and asthma, 5 cancer 6 and cardiovascular diseases 7 have been reviewed recently. The objective of this review is to discuss the role of IL‐32 in autoimmune diseases and, in particular, rheumatoid arthritis (RA) and type 1 diabetes (T1D).…”