Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis.

Ambient fine particulate matter (PM 2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM 2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investigated. In the study, IL-6 receptor (IL-6R)-deficient (IL-6R^-/-) and wildtype littermate (IL-6R^+/+) mice were exposed to concentrated ambient PM 2.5 (CAP) or filtered air (FA), and their pulmonary and metabolic responses to these exposures were analyzed. Our results demonstrated that IL-6R deficiency markedly alleviated PM 2.5 exposure-induced increases in lung inflammatory markers including the inflammation score of histological analysis, the number of macrophages in bronchoalveolar lavage fluid (BALF), and mRNA expressions of TNFα, IL-1β and IL-6 and abnormalities in lung function test. However, IL-6R deficiency did not reduce the hepatic insulin resistance nor systemic glucose intolerance and insulin resistance induced by PM 2.5 exposure. Our findings support the crucial role of IL-6 signalling in the development of pulmonary inflammation and dysfunction due to PM 2.5 exposure but question the putative central role of pulmonary inflammation for the extra-pulmonary dysfunctions following PM 2.5 exposure, providing a deep mechanistic insight into the pathogenesis caused by PM 2.5 exposure. [Display omitted] • IL-6R deficiency alleviates PM 2.5 exposure-induced pulmonary dysfunction. • IL-6R deficiency aggravates PM 2.5 -induced glucose intolerance and insulin resistance. • PM 2.5 induces adipose hypertrophy and inflammation in WT and IL-6R deficient mice. • IL-6R deficiency reduces PM 2.5 -induced pulmonary but not extra-pulmonary inflammation. [ABSTRACT FROM AUTHOR]