Immune Netw.  2014 Jun;14(3):123-127. 10.4110/in.2014.14.3.123.

Interleukin-32 in Inflammatory Autoimmune Diseases

• Kim S

• KMID: 2168023
• DOI: http://doi.org/10.4110/in.2014.14.3.123

Abstract

Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha) and IL-6 and its expression is elevated in various inflammatory autoimmune diseases, certain cancers, as well as viral infections. IL-32 gene was first cloned from activated T cells, however IL-32 expression was also found in other immune cells and non-immune cells. IL-32 gene was identified in most mammals except rodents. It is transcribed as multiple-spliced variants in the absence of a specific activity of each isoform. IL-32 has been studied mostly in clinical fields such as infection, autoimmune, cancer, vascular disease, and pulmonary diseases. It is difficult to investigate the precise role of IL-32 in vivo due to the absence of IL-32 gene in mouse. The lack of mouse IL-32 gene restricts in vivo studies and restrains further development of IL-32 research in clinical applications although IL-32 new cytokine getting a spotlight as an immune regulatory molecule processing important roles in autoimmune, infection, and cancer. In this review, we discuss the regulation and function of IL-32 in inflammatory bowel diseases and rheumatoid arthritis.

Keyword

Cytokine; Inflammatory diseases; Inflectional immune responses; Immune cell differentiation; Inflammatory cancer

MeSH Terms

Animals
Arthritis, Rheumatoid
Autoimmune Diseases*
Clone Cells
Cytokines
Inflammatory Bowel Diseases
Interleukin-6
Lung Diseases
Mammals
Mice
Rodentia
T-Lymphocytes
Tumor Necrosis Factor-alpha
Vascular Diseases
Cytokines
Interleukin-6
Tumor Necrosis Factor-alpha

Figure

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  Figure 1 Schematic drawing of IL-32 in mucosal epithelial cells after pathogen infection. Mucosal epithelial cells-released IL-32 stimulates monocytes to produce inflammatory mediators and also differentiates monocytes into macrophage or dendritic cell (DC) like. The macrophages and DC like cells release inflammatory cytokines such as TNFα, IL-1β, and IL-6. Inflammatory mediators-released from the macrophages and DC like cells in the inflamed area recruit and proliferate T-cells resulted in protecting the host against the pathogens and clearing the infections. However, the recruited various immune cells-produced inflammatory cytokines in the absence of endogenous immune suppressor provokes a large number of neutrophil infiltration. Mucosal tissue damages in IBD and CD occur in consequence of the neutrophil proteinases released from the infiltrated neutrophil.

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  Figure 2 The effects of IL-32 in rheumatoid arthritis (RA). An unknown mechanism triggers rheumatoid arthritis (RA) although anti-cytokine therapies are very effective to treat RA patients. The influx of various immune cells, monocyte, macrophage, T-cell, neutrophil, osteoclast, and synovial fibroblast cell present in synovial fluid of RA patients. These immune cells produce inflammatory cytokines such as IL-32, IL-1β, IL-6, and TNFα including serine proteinases from neutrophil resulted in bone resorption and joint damage in RA patients.

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  Figure 3 The regulation of IL-32 in vivo. The experiment of microarray in vitro by using A549 stable cells expressing IL-18Rβ (also known as IL-1R7) treated with IL-18 has identified IL-32 induction that is indicated by blue arrow in Fig. 3 (22). However, the regulation of IL-32 in vivo is the downstream of IFNγ. Th2 immune response is induced by IL-18 after helminth infection whereas interacellular pathogens such as virus, M. Tuberculosis M. Leprae triggers Th1 immune response through IL-12/IL-18. Th1 T-cells and natural killer cells-released IFNγ plus viral RNA are potent inducers of IL-32 through activation of acquired immunity whereas infection directly releases proteinase 3 (PR3) from neutrophils. PR3 cleaves IL-32, TNFα, and IL-1β and enhances these cytokine activities. The unrestrained innate and acquired immunity provoke local inflammation via cross induction of cytokine is involved in IL-32-related inflammatory disorders.

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