Soluble interleukin-6 receptor level reflecting the illness activity in bipolar disorder

To the Editor

A growing body of evidence supports immune dysregulation related to illness activity in bipolar disorder. However, longitudinal reports exploring intra-individual differences in cytokines and cytokine receptors across different polarities and various symptomatic severities of affective episode are lacking (Munkholm et al., 2012; Tsai et al., 2012). Therefore, we present the follow-up of a male patient with bipolar disorder to evaluate the relationship between illness activity and the alteration of immunological parameters in circulation. This physically healthy bipolar patient first experienced a manic episode at the age of 22. Unfortunately, the affective episodes recurred at approximately 3-month intervals since the age of 45, even though he was fully compliant with lithium and valproate. He had been treated with a combination of valproate 1200 to 500 mg/day, carbamazepine 600 to 800 mg/day and olanzapine 5 to 7.5 mg/day from age 47. He provided overnight fasting venous blood between 8:30 and 09:30h every three weeks whilst euthymic to measure the levels of soluble interleukin-6 receptor (sIL-6R), sIL-2R, IL-1 receptor antagonist, and soluble tumor necrosis factor-α receptor type 1. Furthermore, when he had scores on Young Mania Rating Scale (YMRS) >4 or Hamilton Depression Rating Scale-21 (HAMD-21) > 6, the blood samples were collected weekly until YMRS<5 and HAMD <7. When blood was taken, the physical health was re-assessed to rule out any condition possibly affecting immunity. We finally obtained 32 blood samples within 63 weeks. In this period, his body mass index ranged 23.4 to 24.8 kg/m². Pearson’s correlation analysis showed that only sIL-6R levels were significantly correlated to YMRS scores (γ= 0.52, p= 0.002) and to HAMD scores (γ= -0.43, p= 0.015) as shown in Figure 1.

Figure 1.

The sIL-6R levels and scores on YMRS or HAMD during 63 weeks follow-up.

It appears that the plasma sIL-6R level increases with manic severity and decreases with depression in bipolar disorder. Furthermore, peripheral sIL-6R levels may reflect illness activity of bipolar disorder in opposite polarities. Normally circulating sIL-6R is undetectable. However, because chronic inflammation may occur in bipolar disorder, the increased production of sIL-6R persists and could be detectable in bipolar patients (Tsai et al., 2012). The concentration of sIL-6R may be unrelated to medication status in bipolar disorder (Modabbernia et al., 2013). The present findings suggest that peripheral sIL-6R level is a potential indicator of affective severity for both poles of the illness in medicated patients with bipolar disorder.