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The aim of this study was to examine the relationships between cytokines, depression, and pancreatic cancer.A total of 75 individuals were recruited from two New York City hospitals (a cancer center and a psychiatric hospital) and composed of four subgroups: patients with adenocarcinoma of the pancreas who did (n= 17) and did not (n= 26) have a diagnosis of Major Depressive Episode (MDE), and healthy participants with (n= 7) and without (n= 25) MDE. All individuals completed a battery of self-report measures. Sera was assayed using Meso Scale Discovery techniques to measure the following pro-inflammatory and anti-inflammatory cytokines: IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12p70, IFN-gamma, TGF-beta, and TNF-alpha; we also calculated the IL-2/IL-4 ratio.Pancreatic cancer patients had significantly higher levels of IL-6 and IL-10 and significantly lower TGF-beta levels than healthy participants. When the sample was divided into those with and without MDE, the groups only differed with regard to serum IL-6 levels. No significant cancer and depression interaction effect was observed. Severity of depressive symptoms was also significantly correlated with IL-6,rs= 0.28 andp= 0.02, whereas hopelessness was associated with IFN-alpha,rs= 0.34 andp= 0.006. Pain, fatigue, and sleep disturbance were associated with several of the cytokines assayed including IL-1beta (pain intensity), IL-4 (pain intensity and overall sleep quality), IL-12p70 (pain intensity), and TGF-beta (fatigue intensity), but anxiety was not associated with any of the cytokines assayed.This study demonstrated an association between depression and IL-6, but not with other cytokines. Moreover, IL-6 was not significantly associated with other measures of psychological distress (anxiety and hopelessness) or with symptom distress (pain, fatigue, and sleep quality), although some cytokines assayed were associated with specific symptoms. The implications of these findings for the etiology and treatment of depression in pancreatic cancer patients are discussed.