Early activation of p38 mitogen activated protein kinase is associated with interferon-alpha-induced depression and fatigue.

Cytokine-induced stimulation of p38 mitogen activated protein kinase (MAPK) has been shown to influence behaviorally-relevant pathophysiologic pathways including monoamine neurotransmission and neuroendocrine function and thus may contribute to behavioral changes that occur during chronic administration of the innate immune cytokine, interferon (IFN)-alpha. Accordingly, in the current study, phosphorylation (activation) of intracellular p38 MAPK in peripheral blood lymphocytes was analyzed by flow cytometry every 2 h for 12 h following the initial injection of IFN-alpha in eleven patients with chronic hepatitis C. Hourly assessments of plasma concentrations of adrenocorticotropic hormone, cortisol and interleukin-6 were also obtained.

Effects of interferon-alpha on rhesus monkeys: a nonhuman primate model of cytokine-induced depression.

Background: Interferon (IFN)-alpha is an innate immune cytokine that causes high rates of depression in humans and therefore has been used to study the impact of cytokines on the brain and behavior. To establish a nonhuman primate model of cytokine-induced depression, we examined the effects of IFN-alpha on rhesus monkeys.

Methods: Eight rhesus monkeys were administered recombinant human (rHu)-IFN-alpha (20 MIU/m(2)) or saline for 4 weeks in counterbalanced fashion, and videotaped behavior, as well as plasma and cerebrospinal fluid (CSF), were obtained at regular intervals to assess behavioral, neuroendocrine, immune, and neurotransmitter parameters.

Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress.

Objective: The authors sought to determine innate immune system activation following psychosocial stress in patients with major depression and increased early life stress.

Method: Plasma interleukin (IL)-6, lymphocyte subsets, and DNA binding of nuclear factor (NF)-kB in peripheral blood mononuclear cells were compared in medically healthy male subjects with current major depression and increased early life stress (N=14) versus nondepressed male comparison subjects (N=14) before and after completion of the Trier Social Stress Test.

Results: Trier Social Stress Test-induced increases in IL-6 and NF-kappaB DNA-binding were greater in major depression patients with increased early life stress and independently correlated with depression severity, but not early life stress.

Promoter polymorphisms of the interferon-alpha receptor gene and development of Interferon-induced depressive symptoms in patients with chronic hepatitis C: preliminary findings.

Background: Interferon (IFN)-alpha treatment frequently induces depression, which can impair quality of life and reduce treatment adherence. Defining relevant risk factors for IFN-alpha-induced depression is essential for designing preventative treatment strategies.

Objective: The purpose of the present study was to determine whether promoter polymorphisms of -408C/T, -3C/T and GT repeat dinucleotide microsatellite in the IFN-alpha/beta receptor 1 (IFNAR1) gene are associated with the development of IFN-induced depression.