Determination of a Possible Benefit of 4-Aminoquinoline Drugs to Reset Post-Acute Inflammation in Old Age

Abstract

Persisting systemic inflammation of low amplitude is frequently found in elderly people and is a contributary factor to several components of the frailty phenotype, particularly sarcopenia, low mood and higher levels of dependency on others for essential activities, as well as higher all-cause mortality. Older patients with such “inflammaging” have raised baseline concentrations of several pro-inflammatory cytokines in peripheral blood, 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. The purpose of this chapter is to provide a summary of the background science of the relationship between ageing, inflammation and frailty, then described the established role of methyl-xanthines, particularly theophylline, as immune modulating drugs, then proceeding to propose 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 suggestion that formal clinical trials should be conducted of chloroquine as an adjunctive immune modulator for “inflammaging” and persisting post-acute inflammation in old age.