Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
European Journal of Medical Research
Published in: European Journal of Medical Research 1/2015

Open Access 01-12-2015 | Review

A panoramic spectrum of complex interplay between the immune system and IL-32 during pathogenesis of various systemic infections and inflammation

Authors: Babar Khawar, Muddasir Hassan Abbasi, Nadeem Sheikh

Published in: European Journal of Medical Research | Issue 1/2015

Login to get access

Abstract

Cytokines have always been of great interest due to their vast potential and participation in the progression and pathogenesis of various ailments. Interleukin-32 (IL-32) is a recently identified cytokine, whose gene is located on human chromosome 16 p13.3, with eight exons and six splice variants (IL-32α to IL-32ζ). IL-32α, the most abundant form, is secreted by different types of cells including T cells, natural killer (NK) cells, monocytes, endothelial cells and epithelial cells. It acts as a preferential mediator and effector of abnormal immune responses to multiple inflammatory and auto immune diseases including rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), etc. It was found to stimulate the induction of various chemokines, pro-inflammatory cytokines including IL-1β, IL-6, IL-8, TNF-α and macrophage inflammatory protein-2 (MIP-2). Hence, IL-32 mediates the crucial interplay among immune system and body cells during pathogenesis of various insults. The aim of the present effort is to summarize the role, mechanism of pathogenesis and potential therapeutic applications of IL-32 in different systemic infections and diseased conditions.
Literature
1.
Navarro-Gonzalez JF, Mora-Fernandez C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 2008;19:433–42.CrossRefPubMed
2.
3.
Dahl CA, Schall RP, He HL, Cairns JS. Identification of a novel gene expressed in activated natural killer cells and T cells. J Immunol. 1992;148:597–603.PubMed
4.
Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat Protoc. 2006;1:581–5.CrossRefPubMed
5.
Kim SH, Han SY, Azam T, Yoon DY, Dinarello CA. Interleukin-32: a cytokine and inducer of TNF-alpha. Immunity. 2005;22:131–42.PubMed
6.
Shoda H, Fujio K, Yamaguchi Y, Okamoto A, Sawada T, Kochi Y, et al. Interactions between IL-32 and tumor necrosis factor alpha contribute to the exacerbation of immune-inflammatory diseases. Arthritis Res Ther. 2006;8:R166.CrossRefPubMedCentralPubMed
7.
Marian E, Baraldo S, Visentin A, Papi A, Saetta M, Fabbri LM, et al. Up-regulated membrane and nuclear leukotriene B4 receptors in COPD. Chest J. 2006;129:1523–30.CrossRef
8.
Kim YG, Lee CK, Oh JS, Kim SH, Kim KA, Yoo B. Effect of interleukin-32-gamma on differentiation of osteoclasts from CD14+ monocytes. Arthritis Rheum. 2010;62:515–23.PubMed
9.
10.
Netea MG, Lewis EC, Azam T, Joosten LA, Jaekal J, Bae SY, et al. Interleukin-32 induces the differentiation of monocytes into macrophage-like cells. Proc Natl Acad Sci. 2008;105:3515–20.CrossRefPubMedCentralPubMed
11.
Heinhuis B, Koenders MI, van Riel PL, van de Loo FA, Dinarello CA, Netea MG, et al. Tumour necrosis factor alpha-driven IL-32 expression in rheumatoid arthritis synovial tissue amplifies an inflammatory cascade. Ann Rheum Dis. 2011;70:660–7.CrossRefPubMed
12.
Heinhuis B, Koenders MI, van de Loo FA, Netea MG, van den Berg WB, Joosten LA. Inflammation-dependent secretion and splicing of IL-32-gamma in rheumatoid arthritis. Proc Natl Acad Sci. 2011;108:4962–7.CrossRefPubMedCentralPubMed
13.
Kang J-W, Choi S-C, Cho M-C, Kim H-J, Kim J-H, Lim J-S, et al. A proinflammatory cytokine interleukin 32-Beta promotes the production of an anti − inflammatory cytokine interleukin − 10. Immunology. 2009;128:e532–40.CrossRefPubMedCentralPubMed
14.
Goda C, Kanaji T, Kanaji S, Tanaka G, Arima K, Ohno S, et al. Involvement of IL-32 in activation-induced cell death in T cells. Int Immunol. 2006;18:233–40.CrossRefPubMed
15.
Meyer N, Zimmermann M, Burgler S, Bassin C, Woehrl S, Moritz K, et al. IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis. J Allergy Clin Immunol. 2010;125:858–65.CrossRefPubMed
16.
Maestrelli P, El Messlemani Ah, De Fina O, Nowicki Y, Saetta M, Mapp C, et al. Increased expression of heme oxygenase (HO)-1 in alveolar spaces and HO-2 in alveolar walls of smokers. Am J Respir Crit Care Med. 2001;164:1508–13.CrossRefPubMed
17.
Netea MG, Azam T, Ferwerda G, Girardin SE, Walsh M, Park JS, et al. IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1Beta and IL-6 production through a caspase 1-dependent mechanism. Proc Natl Acad Sci U S A. 2005;102:16309–14.CrossRefPubMedCentralPubMed
18.
Saetta M, Baraldo S, Corbino L, Turato G, Braccioni F, Rea F, et al. CD8+ ve cells in the lungs of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:711–7.CrossRefPubMed
19.
Li W, Sun W, Liu L, Yang F, Li Y, Chen Y, et al. IL-32: a host proinflammatory factor against influenza viral replication is upregulated by aberrant epigenetic modifications during influenza A virus infection. J Immunol. 2010;185:5056–65.CrossRefPubMed
20.
Nold MF, Nold-Petry CA, Pott GB, Zepp JA, Saavedra MT, Kim SH, et al. Endogenous IL-32 controls cytokine and HIV-1 production. J Immunol. 2008;181:557–65.CrossRefPubMed
21.
Netea MG, Azam T, Lewis EC, Joosten LA, Wang M, Langenberg D, et al. Mycobacterium tuberculosis induces interleukin-32 production through a caspase-1/IL-18/interferon-gamma-dependent mechanism. PLoS Med. 2006;3:e277.CrossRefPubMedCentralPubMed
22.
Joosten LA, Netea MG, Kim SH, Yoon DY, Oppers-Walgreen B, Radstake TR, et al. IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2006;103:3298–303.CrossRefPubMedCentralPubMed
23.
Ferlazzo G, Pack M, Thomas D, Paludan C, Schmid D, Strowig T, et al. Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci U S A. 2004;101:16606–11.CrossRefPubMedCentralPubMed
24.
Screpanti V, Wallin R, Grandien A, Ljunggren HG. Impact of FASL-induced apoptosis in the elimination of tumor cells by NK cells. Mol Immunol. 2005;42:495–9.CrossRefPubMed
25.
Nold-Petry CA, Nold MF, Zepp JA, Kim SH, Voelkel NF, Dinarello CA. IL-32 dependent effects of IL-Beta on endothelial cell functions. Proc Natl Acad Sci. 2009;106:3883–8.CrossRefPubMedCentralPubMed
26.
Dinarello CA, Kim SH. IL-32, a novel cytokine with a possible role in disease. Ann Rheum Dis. 2006; 65:iii61–4.
27.
Park MH, Song MJ, Cho M, Moon DC, Yoon DY, Han SB, et al. Interleukin-32 enhances cytotoxic effect of natural killer cells to cancer cells via activation of death receptor 3. Immunology. 2012;135:63–72.CrossRefPubMedCentralPubMed
28.
Cagnard N, Letourneur F, Essabbani A, Devauchelle VR, Mistou S, Rapinat A, et al. Interleukin-32, CCL2, PF4F1 and GFD10 are the only cytokine/chemokine genes differentially expressed by in vitro cultured rheumatoid and osteoarthritis fibroblast-like synoviocytes. Eur Cytokine Netw. 2005;16:289–92.PubMed
29.
Moon YM, Yoon BY, Her YM, Oh HJ, Lee JS, Kim KW, et al. IL-32 and IL-17 interact and have the potential to aggravate osteoclastogenesis in rheumatoid arthritis. Arthritis Res Ther. 2012;14:R246.CrossRefPubMedCentralPubMed
30.
Xu WD, Zhang M, Feng CC, Yang XK, Pan HF, Ye DQ. IL-32 with potential insights into rheumatoid arthritis. Clin Immunol. 2013;147:89–94.CrossRefPubMed
31.
Muller-Ladner U, Gay S. The role of fibroblast-like synoviocytes in rheumatoid arthritis. Rheumatoid Arthritis. 2006;2:107–21.
32.
Pierer M, Rethage J, Seibl R, Lauener R, Brentano F, Wagner U, et al. Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by Toll-like receptor 2 ligands. J Immunol. 2004;172:1256–65.CrossRefPubMed
33.
Jung YO, Cho ML, Kang CM, Jhun JY, Park JS, Oh HJ, et al. Toll-like receptor 2 and 4 combination engagement upregulate IL-15 synergistically in human rheumatoid synovial fibroblasts. Immunol Lett. 2007;109:21–7.CrossRefPubMed
34.
Kyburz D, Rethage J, Seibl R, Lauener R, Gay RE, Carson DA, et al. Bacterial peptidoglycans but not CpG oligodeoxynucleotides activate synovial fibroblasts by toll-like receptor signaling. Arthritis Rheum. 2003;48:642–50.CrossRefPubMed
35.
Ospelt C, Brentano F, Rengel Y, Stanczyk J, Kolling C, Tak PP, et al. Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: Toll-like receptor expression in early and longstanding arthritis. Arthritis Rheum. 2008;58:3684–92.CrossRefPubMed
36.
Alsaleh G, Messer L, Semaan N, Boulanger N, Gottenberg J-E, Sibilia J, et al. BAFF synthesis by rheumatoid synoviocytes is positively controlled by alpha 5-beta1 integrin stimulation and is negatively regulated by tumor necrosis factor-alpha and toll-like receptor ligands. Arthritis Rheum. 2007;56:3202–14.CrossRefPubMed
37.
Ohata J, Zvaifler NJ, Nishio M, Boyle DL, Kalled SL, Carson DA, et al. Fibroblast-like synoviocytes of mesenchymal origin express functional B cell-activating factor of the TNF family in response to proinflammatory cytokines. J Immunol. 2005;174:864–70.CrossRefPubMed
38.
Zrioual S, Ecochard R, Tournadre A, Lenief V, Cazalis MA, Miossec P. Genome-wide comparison between IL-17A-and IL-17 F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol. 2009;182:3112–20.CrossRefPubMed
39.
Jung MY, Son MH, Kim SH, Cho D, Kim TS. IL-32gamma induces the maturation of dendritic cells with Th1-and Th17-polarizing ability through enhanced IL-12 and IL-6 production. J Immunol. 2011;186:6848–59.CrossRefPubMed
40.
Turner-Brannen E, Choi KYG, Arsenault R, El-Gabalawy H, Napper S, Mookherjee N. Inflammatory cytokines IL-32 and IL-17 have common signaling intermediates despite differential dependence on TNF-receptor 1. J Immunol. 2011;186:7127–35.CrossRefPubMed
41.
Alsaleh G, Sparsa L, Chatelus E, Ehlinger M, Gottenberg JE, Wachsmann D, et al. Research Article Innate Immunity Triggers IL-32 Expression By Fibroblast-Like Synoviocytes In Rheumatoid Arthritis. 2010.
42.
Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–34.CrossRefPubMed
43.
Glocker E, Grimbacher B. Inflammatory bowel disease: is it a primary immunodeficiency? Cell Mol Life Sci. 2012;69:41–8.CrossRefPubMed
44.
45.
46.
Hibi T, Ogata H. Novel pathophysiological concepts of inflammatory bowel disease. J Gastroenterol. 2006;41:10–6.CrossRefPubMed
47.
Peyrin-Biroulet L, Vignal C, Dessein R, Simonet M, Desreumaux P, Chamaillard M. NODs in defence: from vulnerable antimicrobial peptides to chronic inflammation. Trends Microbiol. 2006;14:432–8.CrossRefPubMed
48.
Shioya M, Nishida A, Yagi Y, Ogawa A, Tsujikawa T, Kim-Mitsuyama S, et al. Epithelial overexpression of interleukin-32-alpha in inflammatory bowel disease. Clin Exp Immunol. 2007;149:480–6.CrossRefPubMedCentralPubMed
49.
Kobori A, Yagi Y, Imaeda H, Ban H, Bamba S, Tsujikawa T, et al. Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol. 2010;45:999–1007.CrossRefPubMed
50.
Imaeda H, Andoh A, Aomatsu T, Osaki R, Bamba S, Inatomi O, et al. A new isoform of interleukin-32 suppresses IL-8 mRNA expression in the intestinal epithelial cell line HT-29. Mol Med Rep. 2011;4:483–7.PubMed
51.
Choi J, Bae S, Hong J, Ryoo S, Jhun H, Hong K, et al. Paradoxical effects of constitutive human IL-32 gamma in transgenic mice during experimental colitis. Proc Natl Acad Sci. 2010;107:21082–6.CrossRefPubMedCentralPubMed
52.
Choi J-D, Bae S-Y, Hong J-W, Azam T, Dinarello CA, Her E, et al. Identification of the most active interleukin-32 isoform. Immunology. 2009;126:535–42.CrossRefPubMedCentralPubMed
53.
Andoh A, Yagi Y, Shioya M, Nishida A, Tsujikawa T, Fujiyama Y. Mucosal cytokine network in inflammatory bowel disease. World J Gastroenterol. 2008;14:5154.CrossRefPubMedCentralPubMed
54.
Fantini MC, Monteleone G, MacDonald TT. New players in the cytokine orchestra of inflammatory bowel disease. Inflamm Bowel Dis. 2007;13:1419–23.CrossRefPubMed
55.
Felaco P, Castellani ML, De Lutiis MA, Felaco M, Pandolfi F, Salini V, et al. IL-32: a newly-discovered proinflammatory cytokine. J Biol Regul Homeost Agents. 2008;23:141–7.
56.
Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (COLD) Workshop summary. Am J Respir Crit Care Med. 2001;163:1256–76.CrossRefPubMed
57.
Lopez AD, Shibuya K, Rao C, Mathers CD, Hansell AL, Held LS, et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur Respir J. 2006;27:397–412.CrossRefPubMed
58.
Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;176:532–55.CrossRefPubMed
59.
Luppi F, Franco F, Begh B, Fabbri LM. Treatment of chronic obstructive pulmonary disease and its comorbidities. Proc Am Thorac Soc. 2008;5:848–56.CrossRefPubMed
60.
Chung KF, Adcock IM. Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J. 2008;31:1334–56.CrossRefPubMed
61.
Gan WQ, Man SFP, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004;59:574–80.CrossRefPubMedCentralPubMed
62.
Saetta M, Di Stefano A, Turato G, Facchini FM, Corbino L, Mapp CE, et al. CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157:822–6.CrossRefPubMed
63.
Burrows B, Knudson RJ, Cline MG, Lebowitz MD. Quantitative relationships between cigarette smoking and ventilatory function. AM Rep. 1977;115:195–205.
64.
Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009;374:733–43.CrossRefPubMed
65.
Barnes PJ. The cytokine network in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2009;41:631–8.CrossRefPubMed
66.
Cosio MG, Saetta M, Agusti A. Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med. 2009;360:2445–54.CrossRefPubMed
67.
Saetta M, Mariani M, Panina-Bordignon P, Turato G, Buonsanti C, Baraldo S, et al. Increased Expression of the Chemokine Receptor CXCR3 and Its Ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002;165:1404–9.CrossRefPubMed
68.
Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:2645–53.CrossRefPubMed
69.
Zhu X, Gadgil AS, Givelber R, George MP, Stoner MW, Sciurba FC, et al. Peripheral T cell functions correlate with the severity of chronic obstructive pulmonary disease. J Immunol. 2009;182:3270–7.CrossRefPubMed
70.
Saetta M, Turato G, Maestrelli P, Mapp CE, Fabbri LM. Cellular and structural bases of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;163:1304–9.CrossRefPubMed
71.
Saetta M, Baraldo S, Turato G, Beghe B, Casoni GL, Bellettato CM, et al. Increased proportion of CD8+ T-lymphocytes in the paratracheal lymph nodes of smokers with mild COPD. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20:28–32.PubMed
72.
Bosken CH, Hards J, Gatter K, Hogg JC. Characterization of the inflammatory reaction in the peripheral airways of cigarette smokers using immunocytochemistry. Am Rev Respir Dis. 1992;145:911–7.CrossRefPubMed
73.
Kouzaki H, O'Grady SM, Lawrence CB, Kita H. Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2. J Immunol. 2009;183:1427–34.CrossRefPubMedCentralPubMed
74.
Proud D, Chow CW. Role of viral infections in asthma and chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2006;35:513–8.CrossRefPubMed
75.
Richter A, O'Donnell RA, Powell RM, Sanders MW, Holgate ST, Djukanovic R, et al. Autocrine ligands for the epidermal growth factor receptor mediate interleukin-8 release from bronchial epithelial cells in response to cigarette smoke. Am J Respir Cell Mol Biol. 2002;27:85–90.CrossRefPubMed
76.
Takizawa H, Tanaka M, Takami K, Ohtoshi T, Ito K, Satoh M, et al. Increased expression of transforming growth factor-Beta 1 in small airway epithelium from tobacco smokers and patients with chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med. 2001;163:1476–83.CrossRefPubMed
77.
Ying S, O'Connor B, Ratoff J, Meng Q, Fang C, Cousins D, et al. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J Immunol. 2008;181:2790–8.CrossRefPubMed
78.
Calabrese F, Baraldo S, Bazzan E, Lunardi F, Rea F, Maestrelli P, et al. IL-32, a novel proinflammatory cytokine in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;178:894–901.CrossRefPubMed
79.
Kudo M, Ogawa E, Kinose D, Haruna A, Takahashi T, Tanabe N, et al. Oxidative stress induced Interleukin-32 mRNA expression in human bronchial epithelial cells. Respir Res. 2012;13:19.CrossRefPubMedCentralPubMed
80.
Greene CM, Low TB, O'Neill SJ, McElvaney NG. Anti-proline-glycine-proline or antielastin autoantibodies are not evident in chronic inflammatory lung disease. Am J Respir Crit Care Med. 2010;181:31–5.CrossRefPubMed
Metadata
Title
A panoramic spectrum of complex interplay between the immune system and IL-32 during pathogenesis of various systemic infections and inflammation
Authors
Babar Khawar
Muddasir Hassan Abbasi
Nadeem Sheikh
Publication date
01-12-2015
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2015
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-015-0083-y

Other articles of this Issue 1/2015

European Journal of Medical Research 1/2015 Go to the issue

Retraction Note

Retraction Note: Systematic evaluation of percutaneous radiofrequency ablation versus percutaneous ethanol injection for the treatment of small hepatocellular carcinoma: a meta-analysis

Retraction Note

Retraction Note: Meta-analysis on the efficacy of tourniquet on ankle trauma surgery

Research

Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis knee: a systematic review and network meta-analysis

Research

Clinical impact of circulating miR-26a, miR-191, and miR-208b in plasma of patients with acute myocardial infarction

Research

Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C

Case report

Malpositioned olecranon fracture tension-band wiring results in proximal radioulnar synostosis