The Potential to use Chloroquine and other 4-Aminoquinoline Analogues to Modulate Persisting Inflammation in Old Age

Low-amplitude persisting systemic inflammation is frequently found in elderly people and is causally linked to several markers of frailty, including sarcopenia, low mood and higher dependency, as well as higher all-cause mortality. Older patients with such “inflammation” have raised baseline blood levels of several pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-1 beta, and chronically raised C-reactive protein. There is a clear need to identify interventions, including drugs that can ameliorate such inflammation by helping to re-set the innate immune system to a less inflamed baseline. Several classes of drugs have such properties. In this review the authors have summarized the background science with respect to the relationship between ageing, inflammation and frailty, then described the established role of methyl-xanthines, particularly theophylline, as immune modulating drugs before positing a case for the use of 4-aminoquinolines, such as chloroquine, in a similar role. The probable mechanisms of anti-inflammatory action for those classes of drugs are compared, leading to a proposal that formal clinical trials should be conducted of chloroquine as an adjunctive immune modulator for “inflammaging” and persisting post-acute inflammation in old age.