Inflammatory mediators may reflect a role of systemic inflammation in the neurodegenerative process of Parkinson’s disease (PD). Interleukin-6 (IL-6) and chemokine ligand 5 (CCL5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), have been implicated in neurodegenerative diseases including PD. Serum levels of RANTES and IL-6 of 78 consecutive PD patients and age-matched 80 controls were measured. Patients with PD had higher RANTES and IL-6 levels compared with the controls. We found that serum RANTES levels strongly correlated with Hoehn-Yahr score and disease duration in PD patients. This study indicated that patients with PD have an on-going systemic inflammatory profile where the elevated peripheral production of RANTES may play a role in the neurodegenerative process.

Background Epidemiological data have suggested that tobacco and alcohol consumption were associated with the risk of frailty and falling, but it is yet unclear whether these associations are of a causal nature. Thus, we conducted two-sample Mendelian randomisation analysis using genetic instruments to determine the causal associations of tobacco and alcohol consumption on frailty and falls. Methods Independent instrumental variables strongly (p<5E–09) associated with tobacco and alcohol consumption were obtained from the genome-wide association study (GWAS) and Sequencing Consortium of Alcohol and Nicotine use (up to 2 669 029 participants). Summary statistics of the frailty index (FI, N=175 226) and falling risk (N=451 179) were from the two latest published GWAS datasets on FI and falling risk. Results Using the inverse-variance weighted method, our results showed that genetically determined initiation of smoking was significantly associated with an increased FI (β=0.34, 95% CI=0.29 to 0.40, p=5.48E–33) and risk of falling (OR=1.39, 95% CI=1.30 to 1.50, p=1.01E–20). In addition, the age of initiation of smoking and cigarettes consumption per day was negatively and positively associated with both FI and falls, respectively. Current smokers were prone to having a higher FI and falling risk than individuals who quit smoking. There was no significant causal association between alcohol use and the risk of frailty and falling. Similar results were obtained using other statistical approaches with good stability. Conclusions Our findings demonstrate that tobacco use, but not alcohol drinking, significantly increases the risk of frailty and falling. Future studies are warranted to clarify the underlying physiopathological mechanisms.