Research reportEffects of symptomatic severity on elevation of plasma soluble interleukin-2 receptor in bipolar mania
Introduction
A pathophysiological role of the immune system has been suggested in various psychiatric disorders. There is increasing evidence that schizophrenia (Ganguli and Rabin, 1989; Rapaport et al., 1994a; Hornberg et al., 1995; Maes et al., 1995a; Müller et al., 1997b), major depression (Maes et al., 1995b; Sluzewska et al., 1996), and bipolar mania (Maes et al., 1995a; Tsai et al., 1999a) are characterized by activation of the inflammatory response system (IRS) with increased levels of plasma soluble interleukin-2 receptor (sIL-2R). Likewise, major depression may be accompanied by an increased secretion of interferon-gamma (IFN-γ) (Maes et al., 1994b). Decreased production of IFN-γ was observed in different subtypes of schizophrenia (Wilke et al., 1996), and bipolar affective patients in acute mania along with their subsequent remission (Leu et al., 1998). However, increased plasma soluble interleukin-6 receptor (sIL-6R) levels are found in schizophrenia (Maes et al., 1995a) as well as major depression (Maes et al., 1995b; Sluzewska et al., 1996), but not in bipolar mania (Tsai et al., 1999a). Though plasma levels of sIL-2R may vary with race and environmental influences such as smoking in healthy humans (Tollerud et al., 1994), the circulating sIL-2Rs and sIL-6Rs are more stable immune markers and are readily measured in plasma. Thus, it has been suggested that these immune modulators may vary in different psychotic disorders (Tsai et al., 1999a).
Interestingly, elevation of plasma sIL-2R levels is not present in minor psychiatric disorders, such as panic disorder (Rapaport and Stein, 1994a), social phobia (Rapaport and Stein, 1994b), obsessive compulsive disorder (Maes et al., 1994a), post-traumatic stress disorder (Spivak et al., 1997), anorexia nervosa (Nagata et al., 1999), or stress-induced anxiety (Song et al., 1999). The significant elevation of sIL-2R levels represents a state-dependent effect in bipolar disorder (Rapaport, 1994; Tsai et al., 1999a). Therefore, following our previous report that PHA-induced lymphocyte proliferation in acute mania is significantly higher than that in remission (Tsai et al., 1999a), more data are needed to explore the relationships between plasma sIL-2R levels and bipolar disorder.
Gender, age, and medication status may not affect the plasma levels of sIL-2R and sIL-6R levels in bipolar disorder (Rapaport, 1994; Maes et al., 1995a; Tsai et al., 1999a), yet little is known about the effects of the clinical characteristics of bipolar disorder such as age of onset, presence of psychotic features, length of illness, number of prior episodes, and symptomatic severity on plasma sIL-2Rs and sIL-6Rs. Furthermore, the results of studies investigating plasma sIL-6R levels in bipolar mania are not consistent (Maes et al., 1995a; Tsai et al., 1999a). It is hypothesized that the immune-modulators play a role in bipolar mania. The purposes of this study were: (1) to re-investigate plasma sIL-2R and sIL-6R levels in acute mania along with remission of bipolar disorder with a larger sample size of patients and (2) to examine the influences of the aforementioned clinical characteristics of bipolar disorder on these two immune modulators. The present sample is independent from our prior work (Tsai et al., 1999a) and represents an attempt to replicate and extend the findings of that study.
Section snippets
Subjects
Acute in-patients meeting the DSM-IV diagnostic criteria for bipolar disorder, manic with Young Mania Rating Scale (YMRS, Young et al., 1978) scores of ≥26, and aged ≤45 years were invited to participate. They were rated and diagnosed by two senior psychiatrists with a well-validated semi-structural schedule for Taiwanese psychiatrists, the Psychiatrist Diagnostic Assessment (PDA) (Hwu and Yang, 1988) that has been successfully used in bipolar research and described extensively elsewhere (Tsai
Results
Fifteen male and 16 female manic patients with a mean age of 31.9 years (S.D.=10.0) and 31 (15 male and 16 female) healthy controls with a mean age of 33.1 years (S.D.=8.7) participated in the study. Table 1 displays continuous variables of clinical characteristics in the acute mania and subsequent remission. The plasma sIL-2R levels in subgroups with various categorical variables of clinical characteristics are given in Table 2.
In acute mania, plasma sIL-2R levels in 74.2% (18 medicated and 5
Discussion
To our knowledge, this is the first study to examine the influence of clinical characteristics on plasma levels of sIL-2R along with sIL-6R in bipolar mania and subsequent remission. In contrast to schizophrenia (Hornberg et al., 1995) and depressive disorder (Maes et al., 1995b; Sluzewska et al., 1996) with increased sIL-2R levels as a trait marker, one major finding is that there is an association between plasma sIL-2R levels and severity of mania in bipolar disorder. However, the increased
Acknowledgments
This study was supported by grant NSC 89-2320-B-038-006 and NSC 89-2314-B-038-009 from the National Science Council, Taiwan. The authors thank Dr. Kun-Po Chen for data collection and Mr. Tsung-Yuan Wu for technical assistance.
References (36)
- et al.
Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis
J. Psychiatr. Res.
(1999) - et al.
Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia
Schizophr. Res.
(1995) - et al.
Positive and negative acute phase proteins in affective subtypes
J. Affect. Disord.
(1998) - et al.
Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response
Psychiatry Res.
(1994) - et al.
Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers
J. Psychiatr. Res.
(1995) - et al.
Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression
J. Affect. Disord.
(1995) - et al.
Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs
Psychiatry Res.
(1997) - et al.
Soluble IL-6 receptors in the serum and cerebrospinal fluid of paranoid schizophrenic patients
Eur. Psychiatry
(1997) - et al.
Lymphocyte subset, lymphocyte proliferative response, and soluble interleukin-2 receptor in anorexic patients
Biol. Psychiatry
(1999) - et al.
Increased production of interleukin-2 (IL-2) but not soluble interleukin-2 receptors (sIL-2R) in unmedicated patients with schizophrenia and schizophreniform disorder
Psychiatry Res.
(1996)
Immune parameters in euthymic bipolar patients and normal volunteers
J. Affect. Disord.
Increased serum soluble interleukin-2 receptors in Caucasian and Korean schizophrenic patients
Biol. Psychiatry
The effects of prolonged lithium exposure on the immune system of normal control subjects: serial serum soluble interleukin-2 receptor and antithyroid antibody measurements
Biol. Psychiatry
Immune parameters in rapid cycling bipolar patients before and after lithium treatment
J. Psychiatr. Res.
Indicators of immune activation in major depression
Psychiatry Res.
Elevated levels of plasma interleukin-1 beta in combat-related posttraumatic stress disorder
Biol. Psychiatry
Influence of psychological stress on immune-inflammatory variables in normal humans. Part II. Altered serum concentrations of natural anti-inflammatory agents and soluble membrane antigens of monocytes and T lymphocytes
Psychiatry Res.
Racial variation in serum-soluble interleukin-2 receptor levels: a population-based study of healthy smokers and nonsmokers
Clin. Immunol. Immunopathol.
Cited by (94)
Changes in inflammation with treatment for bipolar II depression: Pilot trial data on differential effects of psychotherapy and medication
2019, Neurology Psychiatry and Brain ResearchThe association between low-grade inflammation and the clinical features of bipolar disorder in Han Chinese population
2019, PsychoneuroendocrinologyFactors affecting time to remission for inpatients with bipolar mania – A naturalistic Taiwanese study
2018, Journal of Affective DisordersCirculating cathelicidin LL-37 level is increased in euthymic patients with bipolar disorder
2018, Journal of Clinical NeuroscienceA systemic review of evidence for the role of inflammatory biomarkers in bipolar patients
2017, Journal of Psychiatric Research