Similar pattern of interleukin-32 in AAT deficient and AAT replete patients with COPD

IL-32 is a newly discovered cytokine produced by T-lymphocytes, monocytes and NK cells that has emerged as an important regulator of innate and adaptive immune responses. Upregulation of IL-32 has been demonstrated mainly in autoimmune diseases and, more recently, in COPD. We performed this study to clarify the role of IL-32 in controlling immune responses in COPD, with a particular interest on the comparison between subjects with a1 antitrypsin (AAT) deficiency and those with normal levels of AAT. IL-32 was quantified by immunohistochemistry in alveolar macrophages and parenchymal lymphoid follicles of 22 patients with severe COPD, 10 A AT deficient (FEV1 =19±2% pred) and 12 A AT replete (18±2%pred), 11 control smokers (102±3%pred) and 9 non smoking controls (108±6%pred). IL-32 was increased in alveolar macrophages of AAT deficient patients (median;range: 99;86-100%) as well as in AAT replete subjects (98;89-100%) as compared to both smoking (57;0-99%) and nonsmoking controls (19;0-48%; all p<0.005). A prominent IL-32 expression was also observed in parenchymal lymphoid follicles, that were rich in B lymphocytes. Indeed, IL-32+ follicles were increased in AAT replete subjects (1;0-6 foll/cm2 ) as compared to both smoking (0;0-2 foll/cm2 ) and nonsmoking controls (0;0-1foll/cm2; p<0.05 for both) and a similar trend was also present in AAT deficient patients (1;0-7; p=0.06 for both). In conclusion, increased IL-32 expression was observed in both AAT deficient and AAT replete subjects with COPD in alveolar macrophages and lymphoid follicles, suggesting that mechanisms responsible for the persistence of immune responses are similar in the two forms of the disease.