Post-cancer fatigue is not associated with immune activation or altered cytokine production

Prolonged fatigue after cancer treatment is common. The pathophysiology of such post-cancer fatigue (PCF) is unknown, although cross-sectional studies suggest increased pro-inflammatory cytokine production. This study investigated the association between cytokine levels and fatigue from the time of treatment to 12 months later.

A representative nested case-control series was derived from a prospective cohort of women treated for early-stage breast cancer, including 13 PCF cases and 15 matched control subjects who recovered uneventfully. Serum levels and in vitro production of the cytokines interleukin (IL)-1α, IL-2, interferon (IFN)-γ, IL-4, IL-6, IL-10, IL-12, and tumour necrosis factor (TNF)-β were measured by multiplex immunoassay in longitudinally collected samples. In addition, serum levels of neopterin and the anti-inflammatory regulators, IL-1 receptor antagonist, sIL-6R, and sTNF-rII, were assayed by enzyme-linked immunosorbent assay. Flow cytometric analysis of activated leukocyte subsets was performed.

No significant differences in any of these parameters were found between cases and control subjects. Cytokine levels and symptoms showed no clear correlation pattern.

The findings in this well-characterised subject group argue against the notion that PCF is mediated by peripheral inflammation.