Cytokine signaling in the modulation of post-acute and chronic systemic inflammation: a review of the influence of exercise and certain drugs.

Abstract

Acute inflammation in response to stimuli such as infection can be of deleterious amplitude and/or duration in some individuals and often tends towards chronicity in older adults. This inflammatory pattern appears to be causally linked to higher all-cause mortality and other adverse outcomes such as frailty, sarcopenia, mood disorders and impaired cognitive function. Patients in this clinical state have a persistent pro-inflammatory cytokine profile. Exercise has been shown to shift baseline levels of tumor necrosis factor (TNF), interleukin-1 (IL-1) and other cytokines to a less inflamed setting, with interleukin-6 (IL-6) playing a key modulating role. Drugs can also modulate innate immune cells and their biochemical networks with a shift to a surveillance pattern. Theophylline and chloroquine are examples of drugs that could have clinical value as immune modulators. For example, theophylline induces a 20 percent fall in TNF and around 200 percent increase in IL-10 production by blood-harvested mononuclear cells, and a fall of about 50 percent in interferon-gamma (IF-γ) release. Pharmacological activity in that domain could be exploited in clinical practice, with the aim of establishing a less pro-inflammatory innate immune milieu after provocations such as infection, trauma or major surgery