Delayed-type hypersensitivity and chronic fatigue syndrome: the usefulness of assessing T-cell activation by flow cytometry--preliminary study.

Chronic fatigue syndrome or benign myalgic encephalomyelitis has been extensively described and investigated. Although numerous immunological abnormalities have been linked with the syndrome, none have been found to be specific. This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with this syndrome. Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans albicans, and then monitoring for a systemic reaction over the following six to forty-eight hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans albicans antigens by three-colour flow cytometry based on CD3, CD4 and either CD69 or CD25. Another useful parameter is the kinetics of neopterin excretion in the urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other. This work is in the spirit of a multifactorial approach to the group of conditions referred to as "chronic fatigue syndrome".

Biochemical correlates of in vivo cell-mediated immune dysfunction in patients with depression: a preliminary report.

We have previously demonstrated that at least 50% of patients with melancholia have impaired cell-mediated immunity (CMI) as assessed by delayed-type hypersensitivity (DTH) skin responses to a standardized battery of antigens. Hypercortisolaemia and increased circulating catecholamines both occur in patients with severe depressive disorders and each has been proposed as a possible mediator of observed immune abnormalities in patients with mood disorders. As part of a larger study, we collected 24 h urine samples from 28 patients with major depression and measured concentrations of urinary free cortisol (UFC), the noradrenaline metabolite dihydroxyphenylglycol (DHPG), adrenaline, and the dopamine metabolite DOPAC. CMI multitest skin testing revealed a reduced or absent response in 54% of subjects. Those with reduced DTH skin responses demonstrated increased urinary adrenaline (P < 0.02), with trends toward increased UFC (P = 0.052) and increased DHPG (P = 0.06). These differences could not be attributed to differences in age or depression severity. Correlational analyses demonstrated inverse associations between the extent of DTH responsiveness and 24 h levels of urinary adrenaline and DHPG, with similar trends evident for UFC and DOPAC. These results suggest that both circulating catecholamines and cortisol may play roles in the reduction of CMI in patients with severe depression.