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.

Keywords: Anti-inflammation; Asthma; Interleukin-32; Pro-inflammation; Therapeutic agent.

Fig. 1

Production of IL-32 and its downstream signaling network. IL-32 is produced by a variety of cells (e.g., NK cells, T cells, monocytes, and epithelial cells), and its production can be stimulated by different cytokines (e.g., TNF-α, INF-α, IL-2, IL-18, and IL-1β). IL-32 synergizes with NOD1 and NOD2 and subsequently induces the production of IL-6 and IL-1β via a caspase-1–dependent signaling pathway. IL-32 can also activate NF-κB signaling through the IκB pathway (via NOD2-MDP or directly acting on IκB) and/or the p38-MAPK pathway

Fig. 2

Potential roles of IL-32 in asthma. Positive effects are presented using black arrows, and negative effects are presented using the T-shaped ends. The expression of IL-32 in endothelial cells is indicated using a yellow arrow [61]. Another yellow-arrow is used to indicate that IL-32 can stimulate anti-inflammatory IL-10 expression in dendritic cells [14]. DC, dendritic cell; IL, interleukin