Dear Sir, Vojdani et al. [1] report that patients with CFS display increased apoptotic cell population. This abnormality, according to the authors, is due to the activation of protein kinase RNA pathway, which inturn, 'could result from disregulated immune system or chronic viral infection' [1]. The latter explanation, however seems unlikely, because no specific virus has been identified in CFS patients, despite extensive research [2]. Special attention, therefore, should mainly be paid to the immune system of CFS patients, because its repeatedly reported abnormalities may help reveal both the aetiology of CFS and an effective treatment against it.

As Vojdani et al. [1] point out, decreased natural killer (NK) cell activity and altered cytokine production characterize CFS patients. These immunological abnormalities, however, may simply reflect the hypocortisolism of CFS patients [3], because the lack of steroid restraint on the immune system may well account for its derangement [3]. In fact, since NK cell activity is directly associated with the circadian rhythm of cortisol [4], the decreased NK  cell activity observed in CFS patients may simply be due to their cortisol deficiency [3]. The latter, additionally, may also explain why the release of tumor necrosis factor alfa has been found to be increased in peripheral blood mononuclear cell cultures from patients with CFS [5], All those cytokines, in fact, have been reported to rise during hypocortisolism [6]. This suggest, therefore, that the cortisol deficiency of CFS patients may play a central role in causing both their immunological abnormalities and, presumably, their elevated apoptotic cells.

In view of the role of hypocortisolism in CFS, Vojdani and coworkers might be interested in determining whether the enhanced apoptosis found in their subjects with CFS could be reduced by giving them  small daily doses of hydrocortisone and fludrocortisone. he latter, notably, already had been reported of great benefit to CFS patients [7]. The rationale for treating CFS patients with the two steroids that are routinely administered to Addisonian patients [8] lies primarily in the fact that no medical condition, except Addison's disease, shares 20 features with CFS. [3]  Five additional symptoms (dizziness upon standing, orthostatic tachycardia, nausea, diarrhoea, and constipation) can be found in both CFS [9] and Addison's disease [8,10,11]. Rather surprisingly, however, despite the staggering similarities between CFS and Addison's disease, as yet no published attempt has been made to treat CFS patients with both hydrocortisone and fludrocortisone.

R. Baschetti (email baschett@intercity.it)
Retired Medical Inspector, Italian State Railways, Padua, Italy