Depression and cytokines in multiple sclerosis

For the last decade the subject of cytokines became a central topic within multiple sclerosis research. Growing evidence suggests that these molecules play an essential role in the pathophysiology of MS, both by regulating aberrant autoimmune responses and by mediating myelin damage.

There are still many doubts about the biological connection between MS and depression and the association between depression and exacerbation. Magnetic resonance imaging delineated neuroanatomic links between mood disordes and MS lesions indicating a greater proportion of temporal MS plaques in the psychiatric group of MS patients.

We examined 40 patients suffering from a relapsing/remitting type of multiple sclerosis and 20 healthy indivinduals matched closely on age and education.

We have identified:

  1. the presence of depression using interview, Hamilton scale, Beck Depression Inventory (self-reported) and General Health Questionnaire-20 (self-reported).
  2. values of IL-2, IL-2 receptors, IL-6, IL-6 receptors in the serum. We used ELISA and the seri were stored in a temperature of -40 C.

The questionnaires and the blood samples were obtained within the duration of a clinical exacerbation and without the patients or the healthy indivinduals receiving any drugs.

Research indicates that MS patients have more depressive disturbances than do the general population and that patients in exacerbation are more depressed than patients in remission.

In the present study 48% of MS patients during clinical exacerbation and 10% of healthy individuals showed depression.

IL-2 is a necessary growth factor for most T cells and has also been implicated in oligodendrocyte proliferation but no inflammation activity has been directly attributed to IL-2. In MS lesions IL-2 has been found to be widespread in the lesions although most frequently detected with perivascular inflammatory cells.

IL-6 has been related to differentiation of the immune response and is also a potent inducer of the acute phase reaction most frequently expressed by perivascular inflammatory cells in acute MS lesions. In lesions characterized by both inflammation and demyelination, in situ hybridization studies indicated that IL-6 was the most widespread expressed cytokine and IL-2 less intensely expressed.

We must mention that the short half lives of cytokines implies that simple determination of their levels in body fluids do not give meaningful information while the identification of their soluble receptors in Elispot assays is much more important.

According to the above mentioned points there must be a connection between IL-6 receptors, acute phase of MS and depression.

The results of our study indicate that:

  1. depression is very common during clinical exacerbation of multiple sclerosis
  2. increased levels of IL-6 and IL-6 receptors during the acute phase of MS
  3. there is an association between increased IL-6 receptors and depression during the exacerbation of multiple sclerosis.

More research should be done in order to investigate the connection between MS, inflammation, depression and cytokines, something that could be very helpful in the therapeutic trials of MS.

MS: multiple sclerosis, IL-2: interleukin 2, IL-6: interleukin-6

Key words: Depression, multiple sclerosis, cytokines.