The association between fatigue and inflammatory marker levels in cancer patients: a quantitative review

Increased cytokine and neopterin levels may be responsible for cancer-related fatigue, the most common complaint among cancer patients. We quantitatively reviewed empirical findings on this topic, focusing on studies not using immunotherapy. PubMed, PsychINFO and BIOSIS were searched for articles published until July 2006. Studies remained unweighted or were weighted according to study quality and sample size. The correlation coefficient r was used for statistical analyses. Heterogeneity among the studies was examined using the I(2) index. Eighteen studies (1037 participants) of moderately high methodological quality were located and statistically analyzed. Most studies measured more than one inflammatory marker, resulting in a total of 58 correlation estimates. In 31 of these, we had to input a null correlation because results had been simply reported as nonsignificant and no further statistical information was available. General analyses based on weighting according to sample size showed a significantly positive correlation between fatigue and circulating levels of inflammatory markers (r=0.11, p<0.0001). Analyses of individual inflammatory markers revealed significantly positive correlations between fatigue and IL-6 (r=0.12, p=0.004), fatigue and IL-1 ra (r=0.24, p=0.0005), and fatigue and neopterin (r=0.22, p=0.0001). Fatigue did not correlate significantly with IL-1 beta (r=0.05, p=0.42) or TNF-alpha (r=0.04, p=0.34). Given its preliminary nature due to the limited available data, this quantitative review showed a positive association between cancer-related fatigue and circulating levels of IL-6, IL-1 ra and neopterin. Future studies examining the relationship between cancer related fatigue and inflammation would benefit from multiple rather than single blood sampling and from repeated daily ratings of the multidimensional nature of fatigue.